Drug-Resistant Cancers

Source: “COT drives resistance to RAF inhibition through MAP kinase pathway reactivation”
Levi A. Garraway et al.
Nature 468(7326): 968-972

Results: Researchers from the Dana-Farber Cancer Institute uncovered specific cellular changes that allow melanoma tumors to become resistant to a previously effective drug.

Why it matters: Targeted cancer drugs, which are designed to block the effects of genetic mutations that drive the growth of cancer, can be life-saving for patients with those mutations. But eventually—whether it takes months or years—every cancer evolves resistance to these drugs. New insight into the genetic changes underlying this process will aid in the design of new drugs and drug combinations that could allow targeted therapies to work longer and maybe even overcome resistance altogether.

Methods: Researchers analyzed the effects of 600 different protein kinases, a type of enzyme, on melanoma tumor cells growing in a dish. They found that overactivity among nine of the protein kinases—including one that had never previously been implicated in cancer—made the cells resistant to a melanoma drug to which they had once been vulnerable. The researchers confirmed the findings by analyzing tissue samples from melanoma patients who became resistant to the drug.

Next steps: The researchers need to confirm their findings in a larger number of patients. They also plan to look for additional mechanisms of drug resistance by expanding their search beyond protein kinases.

Biological Sutures

Cell-seeded fibers might help heal the heart

Source: “Fibrin microthreads support mesenchymal stem cell growth while maintaining differentiation potential”
Glenn Gaudette et al.
Journal of Biomedical Materials Research Part A 96(2): 301-312

Results: Researchers at Worcester Polytechnic Institute developed biological sutures made up of polymer strands infused with stem cells. They showed that the cells can survive on the threads and maintain their ability to differentiate into different cell types. They also showed that the cells remain on the sutures after being sewn through a collagen matrix that mimics tissue.

Why it matters: Animal research suggests that delivering stem cells to damaged cardiac muscle after a heart attack can help heal the heart, but human studies have shown only modest or transient benefits. Researchers hope that new delivery methods will help the cells remain at the injury site in large enough numbers and for a long enough time to exert more substantial effects.

Methods: The sutures are made from hair-thin threads of fibrin, a protein polymer that the body uses to heal wounds. The strands are transferred to a tube filled with stem cells and growth solution; the tube slowly rotates so the stem cells can adhere to the full circumference of the suture. Once populated by cells, the suture is attached to a surgical needle.

Next steps: The research team is now studying the sutures in rats’ cardiac muscle to determine how long the cells remain at the injury site and whether they can help heal tissue.