A Riddle, Wrapped in a Mystery, Inside an Enigma

Winston Churchill was talking about the Russians when he uttered those famous words, but he could just as well have been talking about cancer. At last year’s American Society of Clinical Oncology (ASCO) meeting, the official focus was on seeing personalized cancer medicine translated from a theoretical approach to a practical one. As you will see in this issue of Oncology & Biotech News, success is being realized on this front. PLX4032 is the most promising therapeutic to emerge for advanced melanoma in a long time, and part of its success is due to its targeted approach. Trials have been restricted to patients with the BRAFV600E mutation, which is what PLX032 is designed to target. By excluding patients who are not likely to benefit from the drug, the researchers get a better sense of just how effective this treatment really is. The BRAFV600E oncogene is found in many types of cancer, and it remains to be seen whether PLX4032 will be effective in other tumor types.

Crizotinib, an ALK inhibitor being developed by Pfizer, is another example where a targeted agent is showing impressive activity in a select population of patients. As Dr West points out (page 18), it is only likely to be effective in the small percentage of patients who are ALK-positive.

Provenge, the newly approved immunotherapy for prostate cancer, is another example of how research is moving us closer to achieving the goal of personalized care. The Provenge therapeutic vaccine is individualized for each patient, using the patient’s own dendritic cells to trigger an immune T-cell response against their tumor cells. As we pointed out in April’s Physician’s Financial News, researchers are working on numerous personalized immunotherapy approaches.

In a Newsweek article called “Desperately Seeking Cures” (http://www.newsweek.com/id/238078), the authors discuss how “Frustration is growing with how few seemingly promising discoveries in basic biomedical science lead to something that helps patients.” It is true that most drugs making it to the bedside are not curing patients; some only minimally prolong life, at best. But this does not accurately reflect the progress being made.

Every day brings new biomarker discoveries, giving us a deeper understanding of how varied each cancer type really is. These biomarkers are affecting not only the way we treat disease but also how we establish a diagnosis and assess prognosis. If we are ever to cure cancer, it will likely require many different drugs designed to target specific tumor variants.

In addition, we are seeing modification in the design of clinical trials for new drugs, for example, which take into account genetic variation in disease. We are seeing more money and effort being expended to determine why a drug works in some patients but not in others and, once that is understood, to identify new targets in the subpopulation of nonresponders. That is the nature of personalized cancer care.

At this year’s annual ASCO meeting, it will become increasingly clear just how much cancer researchers have taken the message from last year’s meeting to heart and how much progress truly is being made. At the same time, cancer research invokes the old adage, “The more I know, the more I know I don’t know.” With each discovery comes another question. It remains to be seen how close we can come to solving the cancer puzzle.