What Cancers Have in Common: Pushing the Boundaries of Science

A Point of View by Mary J. Savage, Ph.D., scientific director, Companion Diagnostics, Merck

Dr. Mary Savage, like many Merck scientists, translates her passion for biology into therapeutic approaches that make a difference in patients’ lives. This is her personal perspective.

Historically, oncology practice and clinical trial design primarily focused on where the tumor first emerged, such as colon or rectum, lung, breast, and endometrium. This approach follows the logic of the scalpel: pinpointing the location of the tumor first enabled surgical plans.

More recently, there have been significant advances in our understanding of the role of cancer biomarkers in molecular and cellular mechanisms that can drive tumor growth.

Biomarkers are biological molecules (typically comprised of DNA, RNA or protein) found in tissues or blood that can serve as a sign to better understand a condition or disease. Sometimes, the same biomarker is found across many different types of cancer, regardless of where the tumor first developed. Within a specific tumor location, these biomarkers can sometimes differentiate whether the tumor is likely to respond to a given treatment.

As such, these biomarkers have been used to help inform clinical research, accelerating the process of getting targeted medicines to patients where separate trials would take years to conduct. Importantly, in some cases, these features can be assessed using laboratory tests that have long been available. Where a test is either not available, or for research use only, the test manufacturer partners with the drug manufacturer to advance together into regulatory approval by government agencies (such as the FDA) a companion diagnostic assay to ensure safe and effective use of the drug in patients likely to respond.

The goal is to use a deeper understanding of the tumor biology and associated biomarkers to tackle tumor research more precisely; going beyond simply where a tumor arose. Instead, we are learning how to attack a cancer based on its biology at the cellular level. At Merck, efforts are underway to better understand microsatellite instability (MSI) and mismatch repair deficiency (dMMR). These biomarkers are present across tumor types, regardless of the original location of the cancer. The presence of high levels of MSI (MSI-H) or dMMR signifies an underlying problem in a cell's ability to fix errors that occur when DNA replicates. Tumor cells determined to have MSI-H or dMMR harbor hundreds to thousands of mutations.

The ultimate proof of our efforts will manifest as a new generation of cancer medicines: those that follow the logic of biology, not the logic of the scalpel.