My colleague, Dr. Lee Schacter, MD, Executive Medical Director of Oncology and I recently hosted a webinar on Cancer Drug Development Using Molecular Pathology with Dr. Afshin Safavi, Ph.D., founder and Chief Scientific Officer at BioAgilytix, a provider of bioanalytical testing services.
We tackled a hefty subject, covering a brief history of cancer diagnosis and treatment, the use of molecular profiling in oncology drug development, an overview of enabling technologies, regulatory considerations and a discussion of the future of molecular profiling in cancer therapies. We had a great turnout for the live webinar event with lots of follow-up questions for our panel. We wanted to address some of our attendees’ questions in a series of blog posts so all of you could benefit from the feedback. Thanks to all who submitted such great questions!
In this first Q&A post, we’re going to address some of the questions we received around enabling technologies. If you have any additional thoughts or related questions to ask our experts, please share your comments below.
Q #1: In recent years, it has become clear that any one tumor is heterogeneous for driver mutations, often with branched evolution. Since site sampling could misidentify the molecular changes throughout the tumor, and targeted therapies may only be transiently effective, due to other driver mutations in other parts of the tumor, a combination of targeted therapies is prohibitively expensive. How do you see biomarker approaches and targeted therapies addressing these issues?
Dr. Schacter: This is indeed a concern as shown by recent research documenting heterogeneity in non-small cell lung cancer. There is no good simple solution. It seems probable that only mixes of targeted agents will hit the multiple drivers present in heterogeneous tumors. The other approach is to use agents in sequence as new drivers emerge in resistant/dominant clones. Targeted therapies are unlikely to be curative, but by using them in sequence, the goal is to make cancer a chronic disease, managed but not cured, like diabetes or hypertension. In contrast, immune therapies appear to be curative in a subset of patients.
Q #2: Is there a molecular screen to predict redundancy in targeted therapy?
Dr. Safavi: No, we are not aware of a general molecular screen to predict redundancy in a targeted therapy. One may predict possible pathways cells might use to bypass a specific blockade, and then test the theory in vivo or in vitro for up-regulation of possible bypass routes or a general screen for changes. Specific screens for specific pathways are being explored at the research stage; for example, the multiplexed kinase inhibitor bead (MIB) system used by Gary Johnson and his group at the University of North Carolina at Chapel Hill (UNC-CH).
Q #3: How do you start looking after markers in a certain cancer?
Dr. Safavi: This generally begins in an academic or clinical teaching center by demonstrating a correlation between a mutation, up-regulation or other change, and a malignancy. For a predictive marker, it must be addressed whether said change is necessary and sufficient to cause the malignancy, and by determining that reversal of the change prevents malignancy.
Q #4: Do you see any distinct challenges or opportunities in biomarker development for solid vs. liquid tumors?
Dr. Schacter: It is somewhat easier in liquid tumors since the tissue is much more readily available with minimally invasive techniques. The greatest challenge with solid tumors is tissue acquisition.
Martha Bonino is the Director of Strategic Accounts at Clinipace Worldwide.