Three children Alejandro Gutierrez, MD, treated for leukemia during his fellowship at Boston Children’s Hospital still haunt him more than a decade later. One 15-year-old boy died from the toxicity of the drugs he was given; the other two patients went through the whole treatment only to die when their leukemia came back. “That really prompted a deep frustration with the status quo,” Gutierrez recalls. “It’s motivated everything I’ve done in the lab since then.”
Gutierrez, now a researcher in the Division of Hematology/Oncology, has made it his mission to figure out why leukemia treatments cure some patients but not others. And in today’s issue of Cancer Cell, he and 15 colleagues report progress on two important fronts: They shed light on how leukemia cells become resistant to drugs, and they describe how two drugs used in combination may overcome that resistance, offering new hope to thousands of children and adults with leukemia.
Most of the time, cancer cells do a combination of two things: they overexpress genes that drive tumor growth and they lose normal genes that typically suppress tumors. No two tumors are exactly alike, but some combination of these two effects is usually what results in cancer. Now, for the first time, researchers have shown that it’s possible to treat cancer by delivering a gene that naturally suppresses tumors.
Researchers from Boston Children’s Hospital, Brigham and Women’s Hospital and Memorial Sloan Kettering Cancer Center combined their cancer biology and nanomaterials expertise and developed a therapeutic capable of delivering a tumor suppressor gene known as PTEN, the loss of which can allow tumors to grow unchecked.
In several preclinical models, their PTEN–boosting therapeutic was able to inhibit tumor growth. Their findings were published yesterday in Nature Biomedical Engineering. …
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.” …