In Perspective

By David Chao, PhD, President and CEO

Biologists’ desire to understand how cells work at the most basic level has accelerated the development of new therapies in undeniable and unpredictable ways.

This issue’s cover story introduces BioMed Valley Discoveries (BVD), a Stowers organization with the mission of taking basic researchers’ findings from the bench to the bedside. BVD has just launched a human clinical trial to test the safety of a new anticancer drug taking aim at a family of growth-promoting enzymes called ERK. While the results of this and future clinical trials won’t be known for many years, the ERK inhibitor program holds great promise for the treatment of drug-resistant melanoma and other cancers. The history of this program also illustrates how the combination of basic and clinical research can lead to innovative new therapies.

The origins of the ERK story reach back over a quarter century to basic research in an area as far removed from cancer as one could imagine: the mating behavior of baker’s yeast. Baker’s yeast comes in two sexes, and when the two meet, yeast cells undergo a characteristic set of changes in their shape and growth. Using mutant yeast cells with mating defects, researchers were able to map the genes and regulatory circuits governing yeast’s mating habits.

Independently, researchers working with rat cells identified the ERK gene as a key component of the circuitry controlling accelerated growth in response to insulin exposure. The scientists were surprised and delighted to find the ERK gene was closely related to two genes governing mating behavior in yeast. This unexpected connection dramatically accelerated scientists’ understanding of the underlying molecular circuitry in both organisms. When subsequent research showed that mutations in this regulatory circuitry lead to certain types of human cancer, ERK and its related enzymes became attractive targets for anticancer drugs.

Today, a recently approved drug, directed against a close cousin of ERK, has shown a remarkable ability to shrink melanomas. Unfortunately, over time many melanomas become resistant to the drug and resume their cancerous growth. The new BVD drug aims to overcome this resistance and keep the tumor’s growth in check.

Back in the eighties, one would have been hard pressed to anticipate research on amorous yeast might someday influence the development of new cancer therapies.  The serendipitous path from yeast to cancer illustrates just how hard it is to predict the nature and timing of the inexorable benefits of basic research.  As a consequence of science’s unpredictability, successful efforts to improve human health need to strike a prudent balance between basic and disease-focused research. More than a decade ago, Jim and Virginia Stowers founded the institute based on their core belief that basic research will yield long-term, practical benefits for mankind. Just a short while after its founding, the institute is now joined by a sister organization with a complementary charter of performing disease- and drug-focused research. In the pages that follow, I hope you will enjoy learning about how these two organizations are striving to realize Jim and Virginia’s vision of providing Hope for Life®.