Screening a class of recently-developed drug compounds — so-called “CDK inhibitors” capable of blocking CDK7/12/13 proteins — against hundreds of different human cancer cell lines, researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center have found that CDK12 inhibitors pack a particularly lethal punch to Ewing sarcoma, a rare cancer typically affecting children and young adults.
Some individuals were entirely cured of the disease
“Now, in mice, we’ve shown that Ewing sarcoma cells die if CDK12 is knocked out genetically or chemically inhibited,” Stegmaier says. What’s more, her team has discovered that CDK12 inhibition can be combined with another drug, called a PARP inhibitor, to double down on Ewing sarcoma cells.
The revelation that CDK12 inhibition can kill Ewing sarcoma cells brings a surge of hope to the field of pediatric oncology, which has long been challenged to find new drugs against childhood cancers. …
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.
In their study, published in the January issue of the Journal of Experimental Medicine, the researchers describe how chemotherapy or other targeted therapies create a build-up of tumor cell debris, comprised of dead, fragmented cancer cells. In animal models, the team observed that this cell debris sets off an inflammatory cascade in the body and also encourages lingering, living cancer cells to develop into new tumors.
“Our findings reveal that conventional cancer therapy is essentially a double-edged sword,” says co-senior author on the study Mark Kieran, MD, PhD, who directs the Pediatric Brain Tumor Program at Dana-Farber/Boston Children’s and is an associate professor of pediatrics at Harvard Medical School. “But more importantly, we also found a pathway to block the tumor-stimulating effects of cancer cell debris — using a class of mediators called resolvins.” …