On average, only about 5 out of 10 patients receiving a given therapy benefit from it, while some may experience troubling side-effects. Identifying clinically meaningful patient subgroups to remedy this is a key element of the Roche Pharma Early Research and Development (pRED) oncology programs. Miro Venturi, Ph.D., site head for biomarkers and experimental medicine, oncology, says, “We are pursuing tailored biomarker strategies to identify mechanistic and pharmacodynamic as well as selection or stratification markers to improve patient benefit.”
To characterize tumors, Roche employs a broad range of platforms such as genetics, genomics, and protein and cellular phenotyping tools. “Our biomarker discovery efforts start very early in the research process,” explains Dr. Venturi. “First, we formulate predictive biomarker hypotheses by understanding the mechanism of action of our candidate drug and looking broadly at many targets. This requires the adoption of multiplexing technologies. Next, we look for confirmation of the key biomarkers as the most accurate descriptors of appropriate pharmacodynamics and clinical response. Finally, we identify biomarkers of resistance to the drug.”
Finding the appropriate biomarker is difficult. “Some of the challenges are deeply connected to the biology of cancer, especially for new compounds in onco-immunology that stimulate a patient’s immune system,” comments Dr. Venturi. “Because patient responses can vary, it is important to correctly identify both tumor- and patient-specific biomarkers. It is also critical to understand tumor heterogeneity.
“Often a small amount of tumor material—a patient biopsy—is removed and made available for further analysis. Since tumors can be heterogeneous, one needs to consider the limitations of such investigations and have a strategy at hand that allows conducting the analysis in more accessible patient samples or via imaging modalities.”
Biomarker identification also presents the opportunity for development of a companion diagnostic to predict or monitor patients’ response to treatment. As Dr. Venturi notes, “It’s important to start developing biomarkers for use as companion diagnostics as early as possible. Usually, this is done in Phase I trials or earlier. The more specific the biomarker, the more likely it will evolve into a diagnostic.”
Dr. Venturi sees some exciting new developments on the horizon. “In the future, there will be less invasive techniques. For example, it will be possible to characterize cell-free DNA in blood; that is, liquid biopsies will allow surveillance of DNA from tumors. We will still face challenges in identifying and validating companion diagnostics; however, we will have many more tools to do so and a progressively deeper understanding of the biology to build biomarker hypotheses upon.”