Look Who’s Talking

In this monthly feature, we ask members of the physician and research communities to answer a question we pose. The Clinical & Research News video team hit the labs at 65 Lansdowne St. in Cambridge to help us answer this month’s question:

What unanswered question in your field do you think will be solvable in the next 5 to 50 years?

Clinical & Research News also heard from Karen Costenbader, MD, MPH, and Steven Barthel, PhD, who made predictions on everything from rheumatoid arthritis (RA) and personalized medicine to how cancer cells fight the immune system.

Karen Costenbader

Karen Costenbader, MD, MPH Associate Director, BWH Lupus Center

In 5 years, I bet we know how many of the genetic polymorphisms associated with rheumatoid arthritis and systemic lupus erythematosis actually cause disease. Hopefully, we will have worked out many molecular pathways and gene-environment interactions leading to disease and responsible for specific manifestations of diseases (for example, RA joint erosions or lupus nephritis).

In 10 years, maybe we will have figured out "why" women develop lupus 9-10 times more commonly than men do. Probably specific genetic factors and gene-environment interactions will have been identified. We may also have point-of-care personalized testing for many diseases. Genetic/environmental exposure assessment scores will be given out in the office for different disease risks. Hopefully, these will be accompanied by risk modification strategies and even prophylactic medications to prevent disease in the highest risk.

In 20 years, wow...We should know so much more about so many diseases. Personalized disease risk prediction and targeted therapies should be available for many important diseases. Hopefully the gap between those who have access to modern medicine and those who don't won't continue to widen with these advances.

Steven Barthel

Steven Barthel, PhD, Post-Doctoral Research Fellow, Dimitroff Lab

1. How and why cancer cells spread to distinct organs is an important question in understanding late-stage cancer metastasis and in developing treatments to stop it. Recent data indicate that organ selectivity may be conferred by tumor cell adhesive receptors, termed “homing molecules,” which act like molecular addresses to steer cancer cells into a target tissue. Subsequent growth of the cancer within that tissue may be conferred by additional growth-related molecules in the microenvironment.

2. Why are some cancers able to evade and resist being killed by the immune system? Understanding how cancer cells fight the immune system and survive is a key topic that will be better understood over the next decades.

3. How do cancer cells evolve and adapt to resist chemotherapeutic intervention over time? Discerning these processes could lead to more effective treatment regimens by either slowing acquired drug resistance or by targeting multiple tumorigenic molecules at once. Genetic, proteomic and structural approaches are beginning to unravel this mystery.