If you follow cancer research, you almost certainly are frequently frustrated by splashy reports about the latest breakthroughs that turn out to be tiny advances in petri dishes in a lab. From the lab to your doctor’s office, finding a new treatment is usually a process at least a decade long. This August I have read several reports on this type of research sounding full of potential but years away from wide-spread use. But some of it seems worth sharing with readers because it reveals new approaches to research and may offer clinical trial possibilities.
The first study to catch my eye was about inflammatory breast cancer (IBC), lung cancer and bladder cancer - although the types of cancer weren’t featured prominently in the news stories. Mayo Clinic researchers led by Panos Anastasiadis studied the proteins that help cells stick together and cell molecules called microRNAs. They believe they have found a way to reprogram cancer cells to show normal growth by turning off the cell mutations that make cancer cells grow wildly. They think that their research will also help with diagnosis when it is not clear whether a tumor is benign or cancerous.
What researchers are learning is that the old way of thinking about cancer according to its place of origin may not be as important as the type of problems that can occur at the molecular level in a cell. A breast cancer cell and a bladder cancer cell may both have the same genetic mutation, so the same medicine may work for two people with different kinds of cancer. Focusing treatment on the tiny differences at the molecular level is sometimes called precision medicine, a term you will be seeing frequently in the news.
This kind of research helps us understand why two sisters who carry the same BRCA 1 or BRCA 2 mutation may not both get breast cancer. Throughout our lives things happen that damage the DNA in our cells; a BRCA mutation is only one example. Fortunately our cells are smart and can usually fix a problem. It is when a second or third event happens to damage the cell that cancer may start. If one sister escapes a second DNA damaging exposure, she may stay healthy despite the genetic problem passed down in her family.
This research also helps us understand why two women whose breast cancer seems identical in its main features such as its hormone or HER2 status may not have the same results from treatment. At the molecular level there are dozens of cancer subtypes, with more being discovered every day.
Basket trialsWith so many subtypes of cell mutations, it can be hard to find and accrue enough patients for a clinical trial to test a new treatment. It is also possible that some medicines that had poor results in a big generalized trial might work really well with a subgroup. This has led to a new type of trial sometimes referred to as a basket trial. In these trials, research subjects are not organized by the origin of the cancer, but by the molecular subtype. Researcher Pasi Jänne points out, “A lung tumor and a breast tumor with inappropriate activation of the same signaling pathways may share more molecular vulnerabilities with each other than with a lung or breast tumor lacking the same mutations. However, how are such patients to be identified and directed toward appropriate clinical trials? Even the most effective of targeted therapies fail to impress when evaluated in the wrong patient population, as illustrated by early trials with EGFR inhibitors in unselected patients.” The answer is** basket trials,** which accrue patients by molecular mutations, not the cancer’s place of origin.
A basket trial which may be of particular interest to our readers with inflammatory breast cancer or other rare forms of breast cancer is the National Cancer Institute’s NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial. This Phase II trial will start with 10 substudies. Each will analyze a treatment for a particular gene mutation. Eventually researchers plan to add at least 10 more treatments. If your cancer has advanced after at least one type of treatment, this trial might be for you. People with rare cancers are encouraged to apply.
Patients in a clinical trial always receive the current standard of care, so you aren’t missing out on any treatment you would normally be given. However, you may also receive a new treatment that will make a difference for cancer patients everywhere. There are risks and benefits to weigh when entering a trial, but a frank talk with your own doctor and with the trial researchers can help you decide whether a particular trial is right for you. If you decide to try one, whatever happens, you can know that you are advancing science.
For Further Reading:
Redig, A. and Jänne, P. Basket Trials and the Evolution of Clinical Trial Design in an Era of Genomic Medicine. Journal of Clinical Oncology. February 9, 2015_._ Accessed from http://jco.ascopubs.org/content/early/2015/02/03/JCO.2014.59.8433.full August 25, 2015
Ross, J. Mayo Clinic Team finds ‘software’ for turning off cell mutations. August 25, 2015. The Australian. Accessed from http://www.theaustralian.com.au/news/health-science/mayo-clinic-team-finds-software-for-turning-off-cell-mutations/story-e6frg8y6-1227497083383?sv=c74c2a7a041b5e93b7fa6a6c09d39c96 August 26, 2015.
Paddock, C. Reprogramming cancer cells back to normal looks feasible, study shows. Medical News Today August 24, 2015. Accessed from http://www.medicalnewstoday.com/articles/298513.php August 25, 2015
Schleszer. J. Precision Medicine Reaches a New Level. August 12, 2015. OncoTherapy Network. Accessed from http://www.oncotherapynetwork.com/renal-cell-carcinoma/precision-medicine-reaches-new-level?cid=em.otn.82315&GUID=E516FC5C-7604-40FE-85E6-8F7CE4923438&rememberme=1&ts=23082015 August 25, 2015.