Caption: Mutant KRAS protein (white) keeps switch (red/pink) open in active state for GTP (arrow). After treatment with ARS-1620 (blue), switch is trapped in inactive GDP-bound state. Credit: Adapted from Cell. 2018 Jan 25;172(3):578-589.
Of the more than 1.7 million Americans expected to be diagnosed with cancer this year, nearly one-third will have tumors that contain at least one mutation in the RAS family of genes . That includes 95 percent of pancreatic cancers and 45 percent of colon cancers. These mutations result in the production of defective proteins that can drive cancer’s uncontrolled growth, as well as make cancers resistant to therapies. As you might expect, RAS has emerged as a major potential target for fighting cancer. Unfortunately, it is a target that’s proven very difficult to “hit” despite nearly three decades of work by researchers in both the private and public sectors, leading NIH’s National Cancer Institute to begin The RAS Initiative in 2013. This important effort has made advances with RAS that have translational potential.
Recently, I was excited to hear of progress in targeting a specific mutant form of KRAS, which is a protein encoded by a RAS gene involved in many lung cancers and some pancreatic and colorectal cancers. The new study, carried out by a pharmaceutical research team in mouse models of human cancer, is the first to show that it is possible to shrink a tumor in a living creature by directly inhibiting mutant KRAS protein .
When most people think about cancer treatments, what typically come to mind are the side effects of traditional chemotherapy: cardiac, liver, and renal toxicity; hair loss; nausea; fatigue—just to name a few. These side effects occur because the cancer drugs damage not just cancer cells, but healthy cells as well. “Targeted” cancer therapy, on the other hand, is designed to target just the cancer cells. Some targeted therapies achieve this because they only attack cells with a particular molecular signature; others are directed to the cancer by physical means. Today, I’d like to introduce you to a researcher who’s developing a targeted drug delivery strategy that uses lasers and light activated drug delivery to fight cancer.
Jonathan Lovell, a Canadian-born researcher at the State University of New York at Buffalo (UB) and recipient of the NIH Director’s Early Independence Award, has designed unique nanosized spherical pods—1/1000 the diameter of a human hair—that open when light shines on them and snap shut in the dark. Lovell will fill these pods, also known as liposomes—hollow fat droplets—with anti-cancer drugs. He’ll then inject them into the body, where they’ll circulate, safely and silently: until they’re activated. When Lovell shines a red laser on the tumor, the light triggers the balloons to open and deliver a blast of the drug—only where it is needed. (Red light penetrates human tissue better than other colors.) It’s a terrific example of how bioengineering can bring fresh solutions to longstanding medical challenges.