The State of The Fight
State of the Fight: Lung Cancerby Dr. Charles Rudin
Lung cancer remains, by far, the number one cause of cancer death in the U.S. According to the National Institute of Health, in 2012, more than 226,000 Americans will be diagnosed with lung cancer, and 160,340 will die. The disease kills more people every year than breast cancer, prostate cancer, colon cancer, liver cancer, kidney cancer and melanoma combined. Right now, with no effective screening methods, most lung cancers aren’t diagnosed until they’ve progressed to their late stages, when treatment options are limited. Additionally, lung cancer has a stigma about it: many of the people at risk are current or former smokers, so some assume they’ve brought the disease on themselves, while nonsmokers make up approximately 15% of lung cancer deaths.
Nobody deserves to die from lung or any other cancer. Regardless of cause or stigma, my colleagues and and I are dedicated to developing and testing novel, therapeutic approaches to lung cancer. I am a Professor of Oncology, the Cancer Center Associate Director for Clinical Research and co-director of the Upper Aerodigestive Cancer Program at Johns Hopkins. I am also on the Stand Up To Cancer Epigenetics Dream Team, led by Steve Baylin and Peter Jones.
Our SU2C project has focused on epigenetic therapy, and has involved both laboratory and clinical research. Epigenetics (“above” the genetics) refers to several regulatory mechanisms that determine which genes are turned on or off in a given cell. Unlike mutations in the genes, epigenetic changes specific to the cancer cell are potentially reversible, and we have been testing a combination of drugs that may reverse some of the key tumor-specific epigenetic changes. We have been very excited to see that in some patients, this approach really works, resulting in major tumor shrinkage. In addition, we think that epigenetic therapy may “prime” the cancer to respond positively to subsequent therapies, including more standard chemotherapy or immunotherapy. These ideas are really untested hypotheses at this point, but we have a next set of clinical trials on the launching pad to really test these concepts.
Retired police officer David Gobin, whose story was highlighted in the SU2C telethon earlier this year, is a great example of the potential implications of this concept. David faced a very advanced lung cancer, which was continuing to grow after multiple standard chemotherapies. He was treated with our epigenetic therapy, and then shifted to an investigational immunotherapy – a treatment designed to stimulate the body’s natural immune system to respond to and kill the tumor. With this one-two punch, he has had a remarkable response, with major reduction in his disease that has persisted and continues to improve over many months. While his case is certainly exceptional, it would have been hard to imagine this sort of response just a few years ago. Both of these experimental treatments have only been in testing for lung cancer for a short time.
The simultaneous emergence of multiple novel investigational approaches to lung cancer, several of which are now showing real promise, has made this a particularly exciting time in lung cancer research. It is a time of renewed hope in the field, for both doctors and patients. The lung cancer research community now has lots of interesting and innovative ideas for how to treat genetically distinct subtypes of lung cancer: we have no shortage of ideas, or even of promising drugs to test.
The single biggest challenge in the field currently, in my opinion, is that the responses to these targeted therapies are almost never long-lasting. Several different mechanisms of acquired resistance to these therapies have been described, but the story is essentially similar across many cancer types: initial great response, but of disappointingly short duration. We have begun exploring entirely different approaches, including epigenetic therapy and immunotherapy, that may have activity across multiple types of lung cancer and may lead to longer lasting (and maybe even permanent) disease remissions.
Unfortunately, the funding for lung cancer research, relative to the death toll, is very small in comparison to many other diseases. In the United States, lung cancer receives just $1,400 of federal funding per death, while breast cancer receives more than $19,000 per death, followed by $9,800 for prostate cancer and just under $6,000 for colon cancer.1 This has slowed research in lung cancer, and in particular has slowed the translation of novel approaches into clinical testing. As noted above, we have no shortage of interesting ideas and promising leads in 2012. There is also no shortage of patients eager to help test novel therapies. The speed with which we can follow up on these leads, to figure out which ones are going to have highest impact for the greatest number of patients, is highly dependent on the level of funding.
SU2C has had a transformative influence on the field by bringing together large numbers of leading researchers from institutions around the country, with complementary strengths and expertise, focused around a unified “Big Picture” idea. This funding is different from most other grants, not only in amount but also in kind. Some of these teams include members that were formerly competitors in academic discovery, now working side by side toward a common therapeutic goal. Another distinctive feature of SU2C funding, that is music to my ears, is a consistent focus on the patient. Among everyone, from the lead researchers, to the participants, to the peer reviewers, a continuing mantra has been, “OK, but how does this help the patient with this disease, today?” And that’s exactly where we need to be.
Everyone can get involved in the fight against lung cancer. If you smoke, or know someone who does, encourage them to seek out resources to help them stop. Spread awareness that lung cancer can derive from a variety of causes, including air pollution, asbestos, radon gas, arsenic, nickel, chromium, soot, tar, and other substances. Lastly, if you or someone you know has been diagnosed with lung cancer, participation in therapeutic clinical trials is essential in our fight to find more effective treatments for lung cancer. Clinical research often represents the cutting-edge of modern cancer care. It is truly a new day in the management of lung cancer, yet only a small fraction of patients diagnosed with lung cancer participate in clinical research. I would encourage lung cancer patients to seek out clinical trial options from their doctors, or to consider referral to centers with access to novel therapeutic studies, so we can continue our fight against this deadly disease.
Dr. Rudin is a Professor of Oncology and the Associate Director for Clinical Research for the cancer center at Johns Hopkins, where he also directs the Upper Aerodigestive Cancer Program and serves as Clinical Director of the Hopkins lung cancer SPORE. Dr. Rudin leads the Johns Hopkins FAMRI Center of Excellence in Translational Research focused on tobacco-related disease. He is a member of three graduate training programs, in Clinical & Molecular Medicine, Anti-Cancer Drug Development, and Cancer Epidemiology Prevention, & Control. Awards include the Annals of Oncology Prize for the best article on early phase clinical research published in the previous 2 years, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, election to the American Society of Clinical Investigation, and the 2011 AACR Caring for Carcinoid Award.
1 Uniting Against Lung Cancer. The Funding Gap. http://www.unitingagainstlungcancer.org/research/need