![]() ![]() “But when you attach this drug to it, it gets spotted right away.” “This mutated protein is usually flying under the radar because it’s so similar to the healthy protein,” says Craik. ![]() It also coaxes the cell to recognize the ARS1620-KRAS complex as a foreign molecule. In the new work, the team shows that when ARS1620 – a targeted KRAS drug similar to sotorasib – binds to mutated KRAS, it doesn’t just block KRAS from effecting tumor growth. Shokat, Craik and their colleagues wondered whether there was another way to target KRAS. Sotorasib, however, doesn’t help all patients with KRAS mutations, and some of the tumors it does shrink become resistant and start growing again. His work contributed to the development and approval of sotorasib. But over recent decades, Shokat carried out detailed analyses of the protein and discovered a hidden pocket in mutated KRAS that a drug could block. It often has only one small change that differentiates it from normal KRAS, and doesn’t have a readily visible spot on its structure for a drug to bind. The mutated version of KRAS, which drives the growth of tumor cells, operates inside cells. Instead, most proteins that differentiate tumor cells from healthy cells are inside the cells, where the immune system can’t detect them.įor many years, KRAS – despite how common it is in cancers – was considered undruggable. But when it comes to cancer cells, there are few unique proteins found on their outsides. The immune system typically recognizes foreign cells because of unusual proteins that jut out of their surfaces. “We suspect that this could lead to deeper and longer responses for cancer patients.” Turning Cancer Markers Inside Out “It’s exciting to have a new strategy leveraging the immune system that we can combine with targeted KRAS drugs,” said Charles Craik, PhD, a lead study author and professor of pharmaceutical chemistry at UCSF. Mutated KRAS is also the target of sotorasib, which the Food and Drug Administration (FDA) has given preliminary approval for use in lung cancer, and the two approaches may eventually work well in combination. KRAS mutations are found in about one quarter of all tumors, making them one of the most common gene mutations in cancer. When we put this marker on the protein, it becomes much easier for the immune system,” said UCSF chemist and Howard Hughes Medical Institute Investigator Kevan Shokat, PhD, who helped lead the new work. ![]() “The immune system already has the potential to recognize mutated KRAS, but it usually can’t find it very well. UCSF chemist Kevan Shokat speaks with graduate student Megan Moore in his lab. Then, an immunotherapy can coax the immune system to effectively eliminate all cells bearing this flag. The new therapy, described in Cancer Cell, pulls a mutated version of the protein KRAS to the surface of cancer cells, where the drug-KRAS complex acts as an “eat me” flag. Now, UC San Francisco researchers have developed a drug that overcomes some of these barriers, marking cancer cells for destruction by the immune system. Tumor cells are notoriously good at evading the human immune system they put up physical walls, wear disguises and handcuff the immune system with molecular tricks. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |