Tumors Form Advance Teams to Ready Lungs for Spread of Cancer

Cancer metastasis requires tumor cells to acquire properties that allow them to escape from the primary tumor site, travel to a distant place in the body, and form secondary tumors. But first, an advance team of molecules produced by the primary tumor sets off a series of events that create a network of nurturing blood vessels for arriving primary tumor cells to set up shop.

In lung cancer, the formation of that niche likely involves immune cells and moderate levels of VEGF and other molecules that promote the formation of new blood vessels, or angiogenesis. But little is known about how the local lining, or endothelial, cells are activated at the niche.

Sandra Ryeom, PhD, assistant professor of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, and colleagues, found that the signaling protein calcineurin upregulates another molecule, Ang-2 that promotes the needed angiogenesis. Hyperactivation of calcineurin in genetically altered mice that lack an inhibitior of calcineurin signaling leads to increased lung metastases. Conversely, inhibiting calcineurin or Ang-2 blocked metastases in lung cells of the mice. The findings are published this week in Cell Reports.

The findings may help shed light on the underpinnings of common cancer metastasis patterns, such as the tendency of prostate cancer to spread to the bones, or melanoma to the brain.

"We demonstrated that the calcineurin pathway is activated specifically in lung endothelium prior to the detection of tumor cells that preferentially and spontaneously metastasize to the lung from our experimental model of flank tumors in mice," says Ryeom.

Also, increased VEGF levels specifically in the lung, and not other organ microenvironments, trigger a threshold amount of calcineurin signaling that activates the Ang2 gene in lung endothelial cells. What's more, they showed that overexpression of the Ang-2 receptor prevents activation of the lung endothelium and inhibits lung metastases in their mouse models. "Our studies provide insights into the mechanisms underlying angiogenesis in the pre-metastatic niche and offer new targets for lung metastases," she says. Because calcineurin acts on the pathways that set up sites of metastasis away from the primary tumor sites, it could be a potential target for future cancer therapies; however it is also active in the immune system. In fact, calcineurin is inhibited by cyclosporine, which is used to combat transplant rejection, so using these types of drugs would be tricky for cancer unless they can be targeted specifically towards endothelial cells. Ongoing studies in the Ryeom lab are investigating whether calcineurin is important for metastases in other organs or whether this pathway is specific for lung metastases. Co authors are Takashi Minami, Tatsuhiko Kodama, Jun-ichi Suehiro, Tsuyoshi Osawa, and Mai Miura, The University of Tokyo; Shuying Jiang, Makoto Naito, Nigata University, Japan; Yuichi Oike, Kumamoto University, Japan; and Keri Schadler, from Penn.

New Mutation Identified, Associated With Better Survival in Lung Cancer Patients

Japanese researchers have identified a mutation associated with a higher incidence of lung cancer in Japanese women who do not smoke, but better survival in lung cancer patients. In a study published today in the journal PLOS ONE, the team from the RIKEN Center for Life Science Technologies shows that the mutation, a single nucleotide polymorphism (SNP) in a gene that protects cells from oxidative stress, is found four times more frequently in women than in men.

Lung cancer is the leading cause of cancer-related deaths in many industrialized countries. Most deaths are due to long-term exposure to cigarette smoke, but non-smokers account for 10 -- 15% of cases.

Dr. Toshihisa Ishikawa and his team analyzed the DNA of patients with primary lung cancer and found that non-smoking Japanese women with two copies of the SNP (-617A) in the NFR2 gene had a markedly higher incidence of adenocarcinoma of the lung, as compared with non-smoking, homozygous males.

Furthermore, they find that both male and female lung cancer patients homozygous for the same SNP in the NRF2 gene survive lung cancer much better.

Nuclear factor erythroid-derived 2 (NF-E2)-related factor (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidation and detoxification genes, and protects normal cells from external toxic challenges and oxidative stress.

Their study also suggests that lung cancer patients harboring a SNP (-617A) allele in the NRF2 gene in combination with the wild-type allele of the MDM2 gene have better prognosis.

"This is the first report providing clinical evidence that homozygous alleles for the SNP (-617A), one of the intrinsic genetic polymorphisms in the NRF2 gene, are associated with the overall survival of lung cancer patients," explains Dr. Ishikawa.

"The study strongly suggests that the presence of homozygous alleles for this SNP is a good prognostic biomarker for the assessment of the overall survival chances of patients with adenocarcinoma, as well as a practical tool for personalized cancer therapy," he concludes.

MicroRNA-31 Might Predict Lung-Cancer Spread
Determining whether a patient's lung cancer has spread to nearby lymph nodes is critical for identifying the most effective therapy, but it usually requires surgery. A new study suggests, however, that measuring levels of a particular molecule in a sample of tumor tissue might accurately answer the question

Researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) have discovered that levels of microRNA-31 (miR-31) predict the spread of the most common form of lung cancer to nearby lymph nodes.

They found that high levels of miR-31 in primary tumor cells predicted lymph node metastasis and poor survival in patients with non-small cell lung cancer (NSCLC). Low expression levels were associated with the absence of metastases and excellent survival.

The findings are published in the journal Clinical Cancer Research.

"Our findings suggest that microRNA expression in the primary lung tumor can estimate whether the tumor has spread to the lymph nodes and can help direct patients to the most appropriate treatment," says principal investigator Tim Lautenschlaeger, MD, a researcher in Radiation Oncology and the OSUCCC -- James Experimental Therapeutics Program.

"Many patients undergo radiation therapy for NSCLC, and particularly those with early stage disease do not routinely undergo surgical staging," he explains. "Staging with positron emission tomography-computed tomography is very useful but not perfect. MiR-31 and other microRNAs can potentially improve our ability to correctly stage these patients.

"Additionally, if we can better estimate invasiveness of each patient's tumor, we could individualize treatment to include the invasive microscopic disease while sparing as much normal tissue as possible."

An estimated 228,190 cases of lung cancer are expected to occur in the United States in 2013, along with 159,500 deaths from the disease. NSCLC accounts for about 80 percent of all lung-cancer patients. Adenocarcinoma is the most common subtype, representing about 40 percent of all lung cancer cases.

MicroRNAs are a class of short, non-coding RNAs that regulate the translation or degradation of messenger RNA and therefore the proteins that cells make. Certain microRNAs are frequently dysregulated in cancer and are associated with tumor initiation and progression.

For this study, Lautenschlaeger and his colleagues examined samples of primary lung adenocarcinoma tissue from 43 patients. They analyzed 10 of these using genome-wide microRNA-sequencing; four of these cases had lymph node metastases and six were free of metastases.

Key technical findings included:

• MiR-31 expression was four times higher in patients with lymph node metastases compared with those without them.
• miR-31 increases cell migration, invasion and proliferation;
• High miR-31 expression predicted poor survival, while low expression was associated with excellent survival.

"Overall, our findings provide a rationale to further evaluate microRNAs as biomarkers to determine which early-stage NSCLC patients treated with radiation therapy might benefit from additional cancer therapy," Lautenschlaeger says.

Milk Thistle in PCT – Tamoxifen (Nolvadex) Still a Liver Killer, Despite Hepatoprotective Effect of Silymarin or Ziziphus

Image 1: Silybum marianum, a medical plant that has been used to treat liver disease for >2,000 years and is a staple in many “post cycle therapy” supplements you can current purchase at your favorite supplement store.

Whether or not you are into “performance enhancing drugs” does not really matter. If you have browsed through the range of one of the myriad of on-line supplement vendors, you will have seen them: the “liver protectors”, “supplements for liver health”, or simply “post-cycle recovery” supplements. The most common ingredient, you will see on the labels of supplements listed in these or similar categories, is silymarin, a flavonoid complex consisting of silybin (the most active component), silydanianin and silychristin, which is either extracted or simply contained in a crude extract of the seeds ofSilybum marianum, a flowering plant of the daisy family, the manufacturers put into their capsules. While scientists still debate whether and for which type of liver disease(s) the use of the obviously non-patentable (you know that this means that no big pharma company will be willing to acknowledge that it works  flavonoid would be an appropriate treatment option (Loguercio. 2011), generations of bodybuilders may actually have saved their live(rs) from the toxic effect of a highly “underrated” liver-killer, the “bros” know as “Tamox” – the Selective Estrogen Receptor Modulator (SERM), Tamoxifen, which is the active ingredient in the “anti-breast-cancer drugs” Nolvadex, Istubal, and Valodex.

In a mouse model (using 60 male Balb/c mice), scientists from Malaysia and the Middle-East conducted a 4-week study on the toxicity of orally administered tamoxifen (20mg/kg; HED ~1.2mg/kg) and the potential protective effect of milk thistle or jujube (Ziziphus, a tree from the buckthorn family, and the ‘silymarin of the middle’ east; Shahat. 2011) extracts at 300mg/kg (HED ~24mg/kg; ~2g for an 80kg human). To this ends, the animals were randomly assigned to one out of four 6 groups (Al-Jassabi. 2011):

1. control - no tamoxifen, no silymarin extract, no ziziphus
2. silymarin control (SC) - no tamoxifen, 300mg/kg silymarin extract, no ziziphus
3. ziziphus control (ZC) - no tamoxifen, no silymarin extract, 300mg/kg ziziphus
4. tamoxifen control (TC) - 20mg/kg tamoxifen, no silymarin extract, no ziziphus
5. tamoxifen silymarin (TS) - 20mg/kg tamoxifen, 300mg/kg silymarin extract, no ziziphus
6. tamoxifen ziziphus (TZ) - 20mg/kg tamoxifen, no silymarin extract, 300mg/kg ziziphus

Now, if you look at the actual effects the admittedly high dose of tamoxifen that was administered to the animals (note: while a 100kg bodybuilder would have to take 160mg to achive the same exposure I have seen obviously idiotic recommendations on various boards which suggest starting off your PCT with doses in the 80mg+ range!), I suppose that those of you who have (for whatever reasons) already used Nolvadex & Co. will probably be shocked.

7-12x elevations in transaminase levels (ALT, GPT, GOT), >70% reductions in antioxidant enzymes (SOD, CAT, GSHpx), on average, and the incredible 68x elevation in lipid peroxidation after “only” four weeks of treatment should make every steroid user reconsider, whether a tamoxifen-based post-cycle protocol does not do more harm than good. After all, one of the most common causes of gynecomastia is liver cirrhosis (Swerdloff. 2011), and you will probably agree that taking a drug to “protect” yourself from the estrogen rebound after (or even in the course of a cycle) which has gynecomastia as a possible side-effect of a side-effect does not really make sense.

Moreover, scientific data on the efficiacy of tamoxifen in the treatment of male hypogonadism (which is basically what steroid users will experience at the end of a “cycle”) is pretty scarce, if not non-existent and from a “scientific point of view” clomifene citrate (clomid) would appear to be the SERM of choice, here (cf. Katz. 2011).

                          Lung cancer research

Why we need research

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure that they work
• We can be sure they work better than the treatments that are available at the moment
• They are known to be safe

The research process

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.
Tests in patients are called clinical trials. The trials and research section has information about what trials are including information about the 4 phases of clinical trials. If you are interested in taking part in a trial, visit our searchable database of clinical trials.
If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team. The database also has information about closed trials and trial results.

 

Causes, risk and prevention

Normal cells become cancer cells because the genes inside them are damaged. In most cases of lung cancer, smoking causes this gene damage. Cancer Research UK is investigating why some smokers get cancer and some don't. If we know more about the genes that are damaged, it may help to prevent lung cancer in the future.
Cancer Research UK's gene research includes finding out

• About the p53 gene and how it is changed in lung cancer
• About the sNRSF gene in the development of small cell lung cancer
• If other genes are involved in the development of lung cancer
• How our genes determine how tobacco smoke affects our lungs
• If our genetic make up affects whether we will smoke and how easy we find it to stop

We are also involved with research into why people smoke and how to help them give up. One team has been looking at combining antidepressant medicines with nicotine replacement. We are also looking at how to stop young people from taking up smoking in the first place.
A large research study across Europe is looking for links between diet and cancer. It is called EPIC (The European Prospective Investigation of Cancer). The study will produce reports on diet and lifestyle and various cancers over the next 10 to 25 years. The researchers have so far reported that eating more fruit may help to reduce the risk of getting lung cancer. But giving up smoking is by far the best way of reducing your risk.

Research into lung cancer screening

Researchers are trying to find better tests to detect lung cancer early. Lung cancer is often picked up on chest X-ray. But by the time it is diagnosed this way, it is often quite advanced. Tests being looked at include

• Spiral CT
• Fluorescence bronchoscopy
• Chemical changes in the body

Spiral CT

A large trial involving more than 50,000 people in the USA reported in 2010 that a type of scan called spiral CT scanning helped to diagnose lung cancer earlier for some people at high risk of developing it. The trial involved people with no lung cancer symptoms who had smoked for at least 10 years and people who had been exposed to asbestos.
The aim behind the screening is to try to detect lung cancer at a stage where it can be operated on. This could help to improve cure rates. But we need more research into the best way of using spiral CT in screening programmes. We also need to find out which groups of people it helps most. Spiral CT scanning is also called low dose helical CT because it uses lower doses of radiation than standard CT scans.
A UK trial called the Lung-SEARCH study is looking at using spiral CT scans combined with a new test called fluorescence bronchoscopy to find lung cancer at a very early stage in people with chronic obstructive pulmonary disease (COPD). COPD means lung disease such as chronic bronchitis and emphysema. People with COPD have a higher risk of lung cancer than people in the general population.

Fluorescence bronchoscopy

Researchers have also been investigating a different way of carrying out a test called a bronchoscopy in people at high risk of lung cancer. This is called fluorescence bronchoscopy and involves using blue and white light to examine the lining of the airways. A UK fluorescence bronchoscopy trial found that this type of bronchoscopy is better than standard bronchoscopy at showing changes in the lining of the airways that may become lung cancer. More research is being carried out to see whether this is a helpful test to use as part of a screening programme.

Chemical changes in the body

The MEDLUNG study is looking for substances in the body (biomarkers) that could show that lung cancer is developing before the person has any symptoms. It is for people who are at high risk. People in the study are having tests because they have symptoms that could be due to lung cancer. The researchers look at samples of sputum, blood and lung tissue to try and find changes in the cells. The aim of this study is to find a biomarker that doctors may be able to use in the future to screen people for lung cancer.
You can find out more about these trials and other screening trials on our clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'screening' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Research into diagnosis and staging

Research is looking at tests to try and improve the diagnosis and staging of lung cancer. One trial is trying to develop a blood test by looking at DNA changes in blood cells and lung cancer cells of people having surgery or chemotherapy treatment for non small cell lung cancer. DNA sometimes changes during cancer treatment. Researchers want to study these changes. They hope it will help them develop a blood test that can detect lung cancer and show how well treatment is working.
A study called the CLUB trial extension is looking for proteins in blood, urine and tissue samples to see if any are linked to lung cancer. Researchers hope to one day develop a blood or urine test to show up these proteins (biomarkers) and help diagnose lung cancer more easily, and spot it earlier if it comes back after treatment.
A trial called Lung-BOOST is looking into whether having tests called endobronchial ultrasound or endoscopic ultrasound, after a CT scan, will help doctors to diagnose and stage lung cancer quicker than standard tests like a bronchoscopy. This could mean that decisions about treatment can be made faster. They also want to find out if these tests are as accurate as the standard tests used to stage lung cancer at the moment. Part of this trial will also look at whether MRI scans are better than CT scans at showing doctors where to take samples during an endobronchial ultrasound or endoscopic ultrasound.
The SPUTNIK study is looking at PET scans and a different type of CT scan called a dynamic CT scan. The researchers want to see which type of scan is better at diagnosing early stage lung cancer.
The Streamline L study is looking to see if a whole body MRI scan may be able to replace a range of tests for diagnosing non small cell lung cancer (NSCLC).
You can find out about trials for lung cancer diagnosis on the clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'tests for diagnosis' from the types of trial. If you want to see all the trials, tick the boxes for closed trials and trial results.

Radiotherapy

Radiotherapy can help to control lung cancer but it does not work well for everyone. Researchers want to develop better tests to work out who will respond to radiotherapy before they start treatment. They also want to see if they can tell who is at the most risk of side effects. The RADAR study is being partly funded by Cancer Research UK. It is looking at genes and proteins (biomarkers) in the blood and cancer tissue of people who are having radiotherapy for lung cancer or who have already finished it. The researchers will also use special PET scans and MRI scans to look at how radiotherapy affects healthy and cancerous lung tissue.
A small study has been looking into planning radical radiotherapy for people with non small cell lung cancer using a 4D CT scan. This scan takes into account the way your chest moves when you breathe. Doctors hope that this will help them minimise the amount of healthy tissue that is exposed to radiotherapy. This study is no longer recruiting patients, and we are waiting for the results.
Another study is looking at a new type of MRI scan called Helium 3 MRI to see how well the lung tissue not affected by cancer is working. The scan shows healthy lung tissue more clearly than other scans. This may help doctors to target the radiotherapy at the cancer more clearly and reduce the risk of scarring of healthy lung tissue due to the radiotherapy (radiation pneumonitis). This type of scan may also help the doctors to see how well radiotherapy works for non small cell lung cancer.
The ASyMS-R study is looking at using mobile phones to help people cope with the side effects of radiotherapy for lung cancer. Patients can use the mobile phones to send information about their symptoms or side effects directly to a computer. The computer alerts a doctor or nurse at the hospital if someone at home needs help. The system is called Advanced Symptom Management System – Radiotherapy (ASyMS-R). This study aims to find out how well the system works and whether it can help patients to have a better quality of life.
Some studies are trying giving radiotherapy in different doses than usual. A higher dose of radiotherapy given over a shorter time than usual is called dose escalated radiotherapy. Some trials are combining different ways of giving radiotherapy with chemotherapy. Having both treatments together is called chemoradiation.
The REST trial is looking at giving radiotherapy after chemotherapy for people who have small cell lung cancer (SCLC) that has spread beyond the lungs (extensive disease). Doctors hope that giving radiotherapy to the chest will help to delay the cancer coming back after chemotherapy.
Doctors know that radiotherapy can help people with non small cell lung cancer (NSCLC). Now with modern radiotherapy techniques, doctors want to find out more. The aim of the LungART trial is to see if giving radiotherapy after surgery helps to stop NSCLC from coming back. The researchers also hope to find out more about the side effects of radiotherapy after lung cancer surgery.
The I-START trial is looking at higher dose radiotherapy for non small cell lung cancer. The researchers think that giving a higher dose of radiotherapy may kill off more cancer cells. But they want to do this without damaging the surrounding healthy tissue such as the food pipe (oesophagus). This early trial aims to find out the maximum safe dose of radiotherapy to the food pipe, how well this dose works, and whether this causes more or worse side effects.
You can find detailed information about research into radiotherapy for lung cancer on our clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'radiotherapy' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Chemotherapy

Chemotherapy is the main treatment for small cell lung cancer and is also commonly used for non small cell lung cancer. Research continues into improving the timing and doses of drugs used. And researchers also hope to find new combinations of drugs that may give better results. Examples of drugs being tested in trials in the UK include

• Ifosfamide
• Carboplatin
• Etoposide
• Vincristine
• Gemcitabine
• Taxol (paclitaxel) 
• Irinotecan
• Mitomycin C
• RAD 001 (Certican)
• Pemetrexed

You can find out more about chemotherapy trials for lung cancer on our clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'chemotherapy' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.
Trials are also looking into other aspects of chemotherapy such as

• Having chemotherapy at home
• Combining chemotherapy with other drugs
• Resistance to chemotherapy
• Proteins that affect how chemotherapy works
• Reducing chemotherapy side effects

Having chemotherapy at home

Researchers are also looking into where patients have treatment. Some hospitals have been looking at giving chemotherapy capsules or tablets, such as topotecan (Hycamtin) capsules, to people in their own homes. One study is looking at giving pemetrexed at home through a drip into a vein. Having treatment at home rather than having to go into hospital may give people a better quality of life.

Combining chemotherapy with other drugs

Researchers also try to combine different types of treatment in new ways to improve results. There are trials combining chemotherapy with thalidomide, a drug that may help to block a cancer's blood supply.
Another trial is comparing the chemotherapy drug pemetrexed with the biological therapy drug erlotinib (Tarceva). There is more information about this trial in the biological treatments section on this page.
Another trial (The TS Study) is looking at whether a substance produced in the body (thymidylate synthase) affects how well the chemotherapy drugs pemetrexed and cisplatin work in people with non small cell lung cancer (NSCLC).
An international trial has added a new type of biological therapy called vandetanib to the chemotherapy docetaxel (Taxotere) for people who had already had chemotherapy for advanced NSCLC. Vandetanib is a cancer growth blocker. The results showed that the combination of the two drugs worked slightly better than docetaxel on its own. We need more research to confirm this.

Resistance to chemotherapy

A common problem with many cancers is that they become resistant to chemotherapy after one or more courses of treatment. In other words, the chemotherapy works well at first, but future courses do not help as much. The CHEMORES study aims to understand more about why chemotherapy to treat lung cancer can stop working. It is looking for changes in blood and tissue samples before and after chemotherapy for lung cancer. It aims to try to find out how cancer cells stop themselves being harmed by chemotherapy.
Research has also involved a drug called decitabine to see if it can make resistant cells respond to chemotherapy drugs again. Researchers at Cancer Research UK are also studying a protein called FGF-2 that may be involved in helping cancer cells survive chemotherapy. They want to find out if it is possible to block this protein.  One trial is testing a drug called LY218308. Researchers want to see if it can help to stop non small cell lung cancer cells becoming resistant to the chemotherapy drug docetaxel.

Proteins that affect how chemotherapy works

A trial is checking if chemotherapy without platinum drugs works better than platinum based chemotherapy in people with high levels of a body protein called ERCC1. It is for people with advanced non small cell lung cancer. ERCC1 helps to repair damage to cancer cells caused by platinum drugs. So the trial wants to find out if different chemotherapy may work better for people who have high levels of ERCC1. You can find out about the ERCC1 trial on our clinical trials database.

Reducing chemotherapy side effects

One trial is looking at reducing chemotherapy side effects. It is recruiting people who are having chemotherapy to help control the growth and symptoms of non small lung cancer. Doctors often use palliative chemotherapy to help lessen the symptoms of non small cell lung cancer. But sometimes chemotherapy can make the leg muscles weak.
The trial is looking at neuromuscular electrical stimulation (NMES), which is a small battery powered device that allows people to exercise their leg muscles while sitting down. We know from research that using NMES has helped people who are not able to exercise their legs due to other medical conditions. The researchers in this trial want to find out how useful NMES is for people with cancer. This trial has now closed and we are waiting for the results.

Radiotherapy and chemotherapy

Some research trials are looking at different ways of giving radiotherapy alongside chemotherapy for lung cancer. One example is the CONVERT trial for small cell lung cancer. Doctors want to find out if the radiotherapy works better if it is given once a day, or twice a day over a shorter period of time.
There is another trial comparing a combination of pemetrexed and cisplatin chemotherapy plus radiotherapy with etoposide and cisplatin chemotherapy plus radiotherapy. This trial is for people with non small cell lung cancer that has spread into structures close to the lung. Doctors want to find out whether pemetrexed or etoposide work better in combination with the other treatments.
A recent meta analysis found that having chemotherapy and radiotherapy together (concurrent treatment) rather than having radiotherapy after chemotherapy (sequential treatment) works better for people with locally advanced non small cell lung cancer.
The SOCCAR trial was also comparing radiotherapy and chemotherapy given together to radiotherapy after chemotherapy. It has finished recruiting and we are waiting for the results to see if it confirms the results of the meta analysis. This trial was for people with advanced lung cancer.
There is more information about these trials on our clinical trials database. Select 'lung' from the dropdown list of cancer types.

Biological treatments

Biological therapies use substances made naturally in the body to kill cancer cells or stop them from growing. Current research in lung cancer is looking at

• Targeting faulty genes
• Erlotinib (Tarceva)
• Gefitinib (Iressa)
• Cetuximab (Erbitux)
• Ramucirumab
• Nivolumab
• Ipilimimab (Yervoy)
• Bevacizumab (Avastin)
• Crizotinib
• Tivantinib
• Pazopanib
• Dacomitinib
• Afatinib
• Dabrafenib
• ADI-PEG 20
• Growth blockers
• Immune boosters
• Cancer vaccines

You can find detailed information about biological therapy trials for lung cancer on our clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'biological therapy' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Targeting faulty genes

In lung cancer, researchers are working on drugs that can correct damage to the p53 gene so that it will work normally again. P53 is a tumour suppressor gene that repairs genes that are damaged and are encouraging cells to grow abnormally. P53 is damaged in a lot of different types of cancer, including lung cancer. This is early research and this treatment is still at the experimental stage.

Erlotinib (Tarceva)

Erlotinib is used to treat patients with advanced non small cell lung cancer that has continued to grow despite having chemotherapy or who are too unwell to have chemotherapy. It is a type of drug known as a tyrosine kinase inhibitor. It works by blocking epidermal growth factor receptors (EGFR) on cells.
Large international trials have found that erlotinib can increase the length of time that the cancer is controlled for some people compared to chemotherapy. Trials are going on in the UK to find the best way of using this drug. Some trials are using erlotinib as a first treatment for advanced non small cell lung cancer, instead of chemotherapy. Some trials are using it combined with chemotherapy or other biological therapy drugs. Doctors also want to find out more about the side effects of erlotinib.

Gefitinib (Iressa)

Gefitinib (Iressa) is used as a treatment for people with locally advanced or metastatic non small cell lung cancer. It is approved by the National Institute for Health and Clinical Excellence (NICE) for people with non small cell lung cancer that is locally advanced or has spread, provided they have not had any other treatment for their cancer. To get the drug, people must test positive for an alteration (mutation) on a growth factor receptor that the drug acts on called epidermal growth factor receptor tyrosine kinase (EGFR-TK).
NICE say that between 10 and 15 people out of every 100 with non small cell lung cancer (10 to 15%) have the EGR-TK mutation. The Scottish Medicines Consortium (SMC) has decided not to recommend gefitinib as a first line treatment within the NHS in Scotland. Research is continuing to try to find the best way of using gefitinib. You can find information about current trials with gefitinib by going to the clinical trials database. Go to the advanced search and pick 'lung cancer' from the dropdown list of cancer types and 'biological therapies' from the dropdown list of treatment types.

Cetuximab (Erbitux)

Another biological therapy drug called cetuximab has also been used, with chemotherapy, in trials for advanced non small cell lung cancer. Cetuximab is a monoclonal antibody which blocks growth factor receptors on cells.  The early results were encouraging, in terms of helping people to live longer. However, in July 2009 the European medicines Agency (EMEA) did not licence it for non small cell lung cancer. Trials are still going on in Europe and the US.

Ramucirumab

Ramucirumab is another monoclonal antibody. Doctors are looking at using this alongside chemotherapy. A trial is comparing ramucirumab and docetaxel chemotherapy with docetaxel alone. This phase 3 trial is for people with advanced non small cell lung cancer (NSCLC) that has come back after platinum chemotherapy. As well as finding out if ramucirumab and docetaxel are better than docetaxel on its own, the researchers want to learn more about the side effects of ramucirumab.

Nivolumab

Another trial is looking at nivolumab for NSCLC that has spread. Nivolumab is a type of monoclonal antibody. The researchers are comparing it with the chemotherapy drug docetaxel.

Ipilimumab (Yervoy)

Ipilimumab is a treatment for advanced melanoma. It works by stimulating T-cells in the body’s immune system. T-cells help to fight cancer and disease. CTLA-4 is a molecule found on the surface of T-cells and it switches them off. Ipilimumab blocks CTLA-4 so that the T-cells stay switched on and active and can attack the cancer cells.
The ICE trial is looking at using ipilimumab with chemotherapy to treat small cell lung cancer that has spread beyond the lung (extensive disease). The trial aims to find out if giving ipilimumab with chemotherapy helps to delay or stop small cell lung cancer coming back. Researchers also want to find out more about the side effects. The CA184156 trial is also looking at ipilimumab with chemotherapy for people recently diagnosed with small cell lung cancer (extensive stage disease).
The IDEATE trial is looking at ipilimumab with carboplatin and paclitaxel chemotherapy for NSCLC that has spread to another part of the body or come back after treatment. The researchers think that combining ibilimumab with chemotherapy may be better than chemotherapy alone to treat advanced NSCLC. The researchers also want to find out how safe this combination of treatment is and to learn more about the side effects.

Bevacizumab (Avastin)

Bevacizumab (also called Avastin) is a monoclonal antibody (MAB) that stops cancers making blood vessels. Bevacizumab is licensed in Europe to treat advanced non small cell lung cancer. It is used in combination with platinum based chemotherapy, such as cisplatin or carboplatin. But this treatment has not been approved by the National Institute for Health and Clinical Exellence (NICE). An American study published in 2012 looked at adding bevacizumab to chemotherapy in people who were older than 65 years with stage 3B or stage 4 non small cell lung cancer. The results showed that adding bevacizumab didn't work any better than the chemotherapy alone.
The CA196005 trial is comparing bevacizumab with a new biological therapy CT-322 alongside treatment with chemotherapy for advanced non small cell lung cancer or NSCLC that has come back after surgery or radiotherapy. Like bevacizumab, CT-322 stops the cancer from growing blood vessels. The aim of this study is to see if the drug combination of paclitaxel, carboplatin and CT-322 helps people with advanced NSCLC more than paclitaxel, carboplatin and bevacizumab.
The BELIEF trial is looking at bevacizumab and erlotinib for NSCLC that has spread and has changes to genes affecting a protein called EGFR. The researchers want to see how well the 2 drugs work for advanced NSCLC and to learn more about the side effects.

Crizotinib 

Crizotinib (Xalkori) is a new type of biological therapy for people with advanced non small cell lung cancer (NSCLC) that has an overactive version of a protein called ALK. ALK plays an important role in controlling cell growth and survival. Crizotinib works by blocking ALK and stopping the growth of cancer cells. About 1 in 20 people with lung cancer have overactive ALK and standard treatments don't work well for them.
There is a trial looking at crizotinib for advanced non small cell lung cancer that has the abnormal ALK gene. The researchers for this phase 3 trial are comparing crizotinib with pemetrexed and either cisplatin or carboplatin.They aim to find out if crizotinib is better than chemotherapy for this type of NSCLC and to learn more about the side effects.

Tivantinib

The MARQUEE trial is looking at a new drug called tivantinib (also known as ARQ 197). It is a type of tyrosine kinase inhibitor. The trial is giving it alongside erlotinib for non small cell lung cancer (NSCLC) that has got worse despite having other treatment. It is for types of NSCLC that are described as non squamous, such as adenocarcinoma or large cell carcinoma. The trial aims to find out if a combination of erlotinib and tivantinib helps people with advanced NSCLC more than erlotinib alone.

Pazopanib

Pazopanib is a type of tyrosine kinase inhibitor (TKI). It is being looked at to help a number of different cancers. The MAPPING-EORTC 08092 study is looking to see if giving pazopanib after chemotherapy can improve treatment for people with advanced non small cell lung cancer.

Dacomitinib

Dacomitinib is a new type of biological therapy. It works by blocking 3 different HER (Human Epidermal Growth Factor) proteins. These proteins are found on lung cancer cells and may help them grow and multiply. The ARCHER trial is comparing dacomitinib with erlotinib to find out which is better at stopping advanced non small cell lung cancer getting worse, and to learn more about the side effects.

Afatinib

The TIMELY trial is looking at afatinib for people with NSCLC who cannot have chemotherapy. Afatinib works by targeting the protein called epidermal growth factor receptor (EGFR). Drugs that target EGFR are more likely to work if the cancer cells have a change (mutation) to a particular gene. People with lung cancer who have never smoked or were light smokers in the past, are more likely to have cancer with this gene change. For that reason, the people taking part in this study are non smokers. They have a type of NSCLC called adenocarcinoma.

Dabrafenib

In a small number of people with NSCLC there is a change in a gene called BRAF. The BRAF gene makes a protein that affects how cancers divide and grow. Dabrafenib blocks the BRAF protein, and is called a BRAF inhibitor. A study is looking at dabrafenib for people with advanced NSCLC, who have a change in the BRAF gene. The researchers want to find out how well this treatment works and its side effects.

ADI-PEG 20

In the laboratory, researchers have found that small cell lung cancer cells are destroyed by removing an amino acid called arginine. Arginine helps with many different jobs in the body, including cell growth. Researchers think that removing arginine, by using the new drug ADI-PEG 20 (pegylated arginine deiminase), may be a way of stopping cancer growth. Researchers for the study looking at ADI-PEG 20 want to see how well it works for small cell lung cancer and how safe it is.

Growth blockers

There is a trial looking at two new drugs combined with chemotherapy. The drugs are growth blockers called ganitumab (AMG 479) and AMG 102. The trial is testing how they work in combination with etoposide and either carboplatin or cisplatin chemotherapy in people with advanced small cell lung cancer. AMG 479 blocks a growth factor receptor called insulin like growth factor receptor (IGFR), and AMG 102 blocks the hepatocyte growth factor receptor. Both drugs have been tested in people with advanced cancer, but this study is looking at how well AMG 479 and AMG 102 work with chemotherapy for small cell lung cancer.
One trial is testing a new drug that blocks a cell signalling system called the PI3K pathway. This trial is looking at BKM120 for people with non small cell lung cancer that has spread. It is for people who have already had chemotherapy. Researchers hope that blocking PI3K proteins may help to stop the lung cancer cells from growing. The aim of the trial is to see if BKM120 helps people who have non small cell lung cancer that has come back, despite having other treatment.
Another trial is looking at a new drug called AUY922 for advanced non small cell lung cancer. We know from laboratory studies that AUY922 can stop cancer cells with high levels of epidermal growth factor receptor (EGFR positive) from growing. In this trial, researchers will compare AUY922 with the chemotherapy drugs pemetrexed and docetaxel.

Immune boosters

The FORTIS-M trial is looking at a new drug called talactoferrin for non small cell lung cancer that has got worse despite treatment. Talactoferrin is a man made version of a natural body substance called lactoferrin. Lactoferrin can help the body fight infections and reduce swelling (inflammation). The trial aims to see if having talactoferrin helps people with non small cell lung cancer that has got worse despite already having 2 other types of treatment.

Cancer Vaccines

Cancer vaccines are designed to help treat cancer by stimulating the immune system to attack the cancer cells. Researchers on the START trial hope that a vaccine called Stimuvax will stop, or slow down, non small cell lung cancer coming back after chemotherapy and radiotherapy. The MAGRIT trial is testing a vaccine called MAGE-A3 ASCI.
The MAGE-A3 ASCI teaches immune cells to recognise a protein called MAGE-A3, found on some types of non small cell lung cancer cells. The theory is that the immune cells will then find and kill the lung cancer cells. Doctors want to find out how well MAGE-A3 ASCI works in stopping or delaying the cancer from coming back after surgery, and learn more about the side effects.
Another trial is testing a vaccine called Lucanix for people who have already had chemotherapy for advanced non small cell lung cancer. The trial aims to find out if having Lucanix after chemotherapy can help people with non small lung cancer to live longer. The researchers also want to learn about the side effects of Lucanix.
A trial is looking at an EGF cancer vaccine alongside chemotherapy for non small cell lung cancer that cannot be removed with surgery. Growth factors are natural body chemicals that control cell growth. They work by plugging into receptors which send signals telling the cells to divide and grow. Non small cell lung cancer cells often have a large number of receptors for a growth factor called EGF. The vaccine in this trial targets EGF and stops it attaching to the cancer cell receptors. The researchers hope that giving the vaccine with chemotherapy will help people with advanced NSCLC to live longer.
You can find detailed information about research into biological therapy for lung cancer on our clinical trials database. Go to the advanced search and choose 'lung' from the dropdown menu of cancer types and 'biological therapy' from the list of treatment types. To see all the trials, tick the boxes for closed trials and trial results.

Research into surgery for lung cancer

There is a research study trying to find ways of helping people to recover more quickly after surgery for early stage lung cancer. Getting back to normal is called rehabilitation. The study is comparing normal care with a rehabilitation programme after surgery to remove lung cancer.
The rehabilitation programme includes exercise, education and guidance on what to eat, and help to stop smoking. The study aims to see if the rehabilitation programme can shorten the time spent in hospital, lower the risk of complications and improve your quality of life.
The ErLaPara study is looking at pain control after having surgery for lung cancer or mesothelioma of the lung. After surgery doctors control pain with a drug that numbs the nerves in the area (local anaesthetic). You usually have this through a thin plastic tube that the surgeon places in your chest near the wound. The doctor usually starts this at the end of surgery. The researchers think that pain may be better controlled if the local anaesthetic was started soon after the start of surgery instead. The people taking part will complete questionnaires about any pain they may have on the first couple of days after surgery.

Smoking after diagnosis

The LungCAST study is looking at whether smoking affects how well lung cancer treatment works. Some researchers believe that smoking after diagnosis may affect the outcome of the lung cancer. They think it could be possible that smoking affects levels of anti cancer treatment in the blood and body tissue.
We know from laboratory research that smoking can make some cancer cells more resistant to chemotherapy. And smoking can affect oxygen levels in cancers, making radiotherapy work less well. We don't know at the moment whether smoking after diagnosis does affect lung cancer treatment. So this study aims to find out whether smoking after a diagnosis of lung cancer affects survival.

Blood thinning drugs

The FRAGMATIC trial is looking at whether blood thinning drugs can improve treatment for lung cancer. Blood clots are quite common in people who have lung cancer. And cancer treatment can increase the risk of blood clots. Dalteparin is a blood thinning drug (anticoagulant), also called Fragmin. It is used to prevent and treat blood clots. Doctors think that dalteparin may also affect how cancer cells spread through the bloodstream, but they don't know for sure.
So this trial gave dalteparin alongside standard treatment for lung cancer to half the people taking part. Researchers are checking to see if it reduced the number of blood clots people got. And they will also see if it can help to stop cancer cells spreading through the bloodstream to other parts of the body.

Statins

Statins are medicines that people usually take to lower their cholesterol. Doctors think that they may also have an effect on cancer cells and they want to find out more about this. The LungStar trial is looking at whether adding a drug called pravastatin to chemotherapy can make it work better for advanced small cell lung cancer.
You can find out more about statin trials for lung cancer on our clinical trials database. Choose 'lung' from the dropdown menu of cancer types and type statin into the search box. Tick the boxes for closed trials and trial results.

Diabetes drugs

Several studies have shown that metformin and other diabetes drugs known as thiazolidedione (TZDs) may slow the growth of lung cancer and help some lung cancer patients live longer. A large study reported at a lung cancer meeting in 2010. It found that people taking anti diabetes drugs are generally less likely to get lung cancer. If they do get it, it is less likely to spread and people also tend to live longer. The reason for this is not known. But some research shows that metformin triggers an enzyme, called AMP activated protein kinase, which blocks a protein called mTOR. mTOR can trigger lung cancer cell growth.
But we need more research before we know how helpful anti diabetes drugs are in the treatment or prevention of lung cancer.

Treating lung cancer symptoms

There is research into relieving symptoms of a blocked airway. In advanced cancer, people sometimes develop a blockage in their airway. This can make you feel breathless. It can also cause noisy breathing, called stridor, which can be upsetting. There are different ways of treating the blockage including radiotherapy to shrink the cancer, or laser surgery to cut away part of the blockage. You may have the more common external beam radiotherapy. Or you may have internal radiotherapy called brachytherapy. This involves putting a sealed radioactive source down a bronchoscope so that it is right next to the blockage. This can work very well.
Another way of relieving breathlessness is by using a stent. This is a hollow tube that is put into the airway during a bronchoscopy. Once the stent is in place, it expands slightly. This eases the blockage and makes it easier to breathe.

A small trial called RESTORE-AIR is looking into using stents to relieve breathlessness in non small cell lung cancer in the windpipe or a main bronchus. Doctors would usually want to give chemotherapy or radiotherapy to reduce the blockage before putting in a stent. But this trial is looking at how much putting a stent in first can help with breathlessness, and how much this can help you to cope with the rest of your treatment. The trial has now closed and we are waiting for the results.
There is information about other trials looking into controlling the symptoms of lung cancer on our clinical trials database.

Radiotherapy for cancer cells in the brain

If lung cancer spreads it often goes to the brain. In this case, doctors often give radiotherapy. But they are not sure if the side effects it causes, such as headaches, feeling tired, or feeling and being sick, cancel out the good effects. The Quartz trial is looking at radiotherapy for people with non small cell lung cancer that has spread to the brain. Everyone on this trial has best supportive care from their health care team, plus treatment with steroids. One group will also have a course of radiotherapy to the brain, while the other will not. Another trial, called TACTIC, is looking into whether it is better to give the biological therapy drug erlotinib (Tarceva) with radiotherapy in this situation. The trial has closed and we are waiting for results.
There is more information about these trials on our clinical trials database.

Research into living with lung cancer

Research into living with cancer can make a real difference to people who are diagnosed. Cancer Research UK is investigating whether counselling or other psychological support helps people to cope with their diagnosis. One research group is specifically investigating the needs of men with cancer.
Depression can be a major problem for people with lung cancer. Doctors want to offer more support to people with lung cancer who have depression. But at the moment they are unsure of the best way to do this. The SMaRT Oncology 3 trial in Scotland is looking at whether it helps to add sessions with a specially trained cancer nurse to the routine treatment for depression.
One trial is developing a new way of providing follow up care after treatment for people who have lung cancer. The trial aims to find out how people feel about having follow up appointments with a specialist nurse instead of their doctor. The nurses help patients and carers to cope with symptoms such as pain or breathlessness, as well as managing problems such as anxiety and depression.
Many people with lung cancer have a cough that can be very distressing and may affect daily life. For example, a cough can make communicating clearly more difficult, and cause poor appetite, sleeplessness, vomiting, severe tiredness, pain, anxiety, fainting, and even loss of control over passing urine. The CLiC study aims to find out how a cough affects quality of life for people with lung cancer. The researchers hope this will help them find better ways of treating and controlling a cough.
The modafanil trial is looking at whether a drug called modafanil can help to reduce the extreme tiredness and exhaustion (fatigue) that some people have with advanced non small cell lung cancer.
The RAPS trial is looking at whether a planned exercise programme can help people recover better after surgery for non small cell lung cancer.
Many people with lung cancer have a condition called cachexia (pronounced kak-ek-see-ah) in which they lose weight and muscle strength. The NOURISH trial is looking at whether a supplement powder given in combination with a support programme can help to stop cachexia. The supplement contains substances that the researchers hope will help to stop muscle breakdown. The aim of this trial is to see if this supplement can prevent people with lung cancer losing weight and muscle strength. It also wants to find out why some people with cancer are more at risk of weight loss than others.
There is a trial looking at a new drug called BYM338 to see if it can help build up muscle and stop weight loss. BYM338 is a drug that blocks an enzyme called myostatin. This enzyme controls muscle growth. By blocking myostatin muscle is able to grow.
There is detailed information about these trials on our clinical trials database.

Symptoms of cancer that has come back

A study is looking at symptoms which could be caused by cancer coming back after treatment. After treatment for cancer of the breast, lung, prostate or bowel, you have follow up appointments with your specialist doctor. But after a few years, if you stay well, these appointments may stop. You are then asked to see your GP if you have any new symptoms, or are worried about anything.

Researchers looked back at the medical notes of people who went to their GP with symptoms some time after cancer treatment. They looked at people whose cancer had come back as well as people whose symptoms were caused by something else. The trial aims to find common symptoms of cancer recurrence to help doctors spot the signs that cancer may have come back. The trial has now closed. You can find details on our clinical trials database. Choose 'lung' from the dropdown menu of cancer types to find lung cancer trials.