Cancer Insights: Molecular profiling unlocks tumor answers

October 27, 2016 | by Sumanta K. Pal, M.D.

Sumanta Pal, M.D. Writing in a recent issue of the Journal of Clinical Oncology, Sumanta K. Pal, M.D., calls attention to the potential use of molecular profiling to define appropriate individualized treatment for bladder cancer patients.

Molecular profiling, unlike any other type of controversial profiling in the news, is an extremely hot topic in cancer medicine today, and it’s going to have a huge impact on patients, physicians and payers. 

So what is molecular profiling?

In its most common application today in the clinic, we take molecular features of a tumor (changes in a protein level, mutations and other alterations in DNA) and link them to potential therapies. The concept is not at all new – decades ago, the HER2 protein was identified as a driver of breast cancer. Not long after, drugs were developed to target patients with increased levels of HER2. Multiple examples of this abound now in literature.

The difference in 2016 is that our ability to profile has increased exponentially. As fast as minutes to hours, we can get the same molecular information about a tumor that would have taken days to months previously. For patients, this means we’ve moved beyond assessment of a single gene or protein – rather, we can assess hundreds at the same time. In certain cancer types, the application is obvious. In lung cancer, for instance, several specific mutations can point the physician toward several corresponding FDA approved therapies.

It can be more nebulous, though. For the many patients I see with advanced bladder cancer (my area of specialty), we are limited to two lines of treatment – chemotherapy and immune-stimulating agents. The sad reality is that most patients will ultimately succumb to the disease, despite these options. One may ask what the role of molecular profiling is in this setting? In my opinion, it is vital. We know that bladder cancer patients harbor a tremendous number of mutations relative to other cancer types. However, due to a limited investment in research, we have no associated therapies that have earned the FDA nod.

Today, however, multiple clinical trials abound for patients with advanced bladder cancer and other less common cancer types who demonstrate specific mutations. Preliminary results from these studies show huge promise, with targeted drugs evoking responses in very aggressive diseases like bile duct cancers – diseases which are otherwise consistently fatal.  With colleagues from around the country, I recently penned an article in the Journal of Clinical Oncology highlighting support for molecular profiling of bladder cancer. My hope is that more widespread use of molecular profiling will give bladder cancer patients options beyond the current standard, which right now entails a bleak prognosis.

So why the controversy around profiling in this setting?

Well, it’s expensive. But as with every new technology, the cost is sure to come down over the coming years. Furthermore, taking a step back, we must consider the options patients have now. If a bladder cancer patient approaches me in clinic after having been through all of the standard treatments, what I will most likely offer is traditional chemotherapy – perhaps not expensive in and of itself, but costly in terms of quality of life and management of attendant side effects.

Furthermore, years of data tell us that additional chemotherapy may do little more than delay tumor growth for a matter of three to six months. In contrast, with an initial investment for molecular profiling, there is a possibility we might spare the patient undue toxicity and offer a more individualized, targeted treatment.

To be fair, molecular profiling is not right for every patient. But when done in the context I have described here, there is perhaps greater potential for benefit (increased tumor shrinkage, greater delay in tumor growth) and the possibility of sparing a patient's exposure to ineffective chemotherapy. With these factors in mind, perhaps this is a kind of profiling we can all agree upon.

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Sumanta Kumar Pal, M.D., is an assistant professor in the Department of Medical Oncology & Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope.

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