Investigators at UC San Diego say that when they blocked a well known signaling molecule that plays a major role in driving colorectal cancer, an escape pathway emerged that allowed tumors to continue to grow.
The pathway they explored, ERK1/2, is a problem for about a third of all colorectal cancer patients, says Petrus R. de Jong, MD, PhD, a co-first author on the paper.
"Since we were genetically deleting the ERK1/2 pathway, we expected to see less cell proliferation," said de Jong. "Instead, the opposite occurred. There was more cell growth and loss of organization within the cells.”
The problem was ERK5, the investigators add. And when that was blocked as well in animal models and cell lines for the disease, the combination approach proved more effective in halting cancer growth.
"If you block one pathway, cancer cells usually mutate and find another pathway that ultimately allows for a recurrence of cancer growth," said co-first author Koji Taniguchi. "Usually, mutations occur over weeks or months. But other times, as in this case, the tumor does not need to develop mutations to find an escape route from targeted therapy. When you find the compensatory pathway and block both, there is no more escape.”
The researchers now plan more animal studies before trying it in humans.