A research team from\u00a0Huntsman Cancer Institute\u00a0at the\u00a0University of Utah (the U)\u00a0reports\u00a0that a groundbreaking\u00a0pathway-targeted therapy could be an effective treatment for certain melanoma patients and fill an\u00a0unmet\u00a0clinical need\u00a0for patients with advanced disease.\u00a0<\/p>\n
Martin McMahon, PhD, senior director of preclinical translation at Huntsman Cancer Institute and professor of dermatology at the U, evaluated an investigative compound of the drug daraxonrasib in\u00a0NRAS-driven\u00a0melanoma.\u00a0NRAS-driven melanoma is an aggressive type of skin cancer\u00a0driven\u00a0by\u00a0mutations\u00a0in the\u00a0NRAS\u00a0gene.\u00a0Daraxonrasib, developed by\u00a0Revolution Medicines,\u00a0targets and inhibits\u00a0RAS, a\u00a0protein\u00a0that drives\u00a0cancer when altered.\u00a0NRAS\u00a0is a subtype of\u00a0RAS\u00a0that\u00a0is\u00a0mutated\u00a0in\u00a0roughly a\u00a0quarter of melanoma\u00a0cases.\u00a0<\/p>\n
The results of\u00a0daraxonrasib\u00a0as a treatment for metastatic pancreatic cancer-in which it doubled\u00a0patients’\u00a0life expectancy\u00a0in a Phase 3 clinical trial-recently\u00a0received a\u00a0standing\u00a0ovation from thousands of physicians\u00a0at the\u00a0American Society of Clinical Oncology Annual Meeting.\u00a0Huntsman Cancer Institute\u00a0was one of just 60\u00a0hospitals\u00a0worldwide who offered\u00a0that\u00a0trial\u00a0(RASolute\u00a0302).\u00a0<\/p>\n
The remarkable success of daraxonrasib in the treatment of pancreatic cancer indicates that we are in an era where even the most recalcitrant\u00a0RAS-driven cancers can be treated. Our data strongly supports the potential future clinical utility of treating patients with\u00a0NRAS-driven melanoma<\/a> with\u00a0daraxonrasib.”\u00a0<\/p>\n Martin McMahon, PhD, senior director of preclinical translation, Huntsman Cancer Institute and professor of dermatology, University of Utah<\/p>\n McMahon and his team evaluated the effectiveness of the\u00a0RAS\u00a0inhibitor in numerous preclinical models, including melanoma samples from patients. The\u00a0results of the study\u00a0have been published in\u00a0Cancer Research, a journal of the\u00a0American Association for Cancer Research.\u00a0<\/p>\n “All our\u00a0NRAS-driven models were very responsive to this\u00a0RAS\u00a0inhibitor. It’s\u00a0actually quite\u00a0rare that we see shrinkage of\u00a0NRAS-driven tumors,” says\u00a0Mona Foth, PhD, research scientist at Huntsman Cancer Institute and first author of the publication. “It’s inspiring to think that these results could potentially lead to a new patient therapy that will help them overcome their disease.”\u00a0<\/p>\n Melanoma is the deadliest form of skin cancer, and their research aims to help fulfill an\u00a0unmet clinical need in patients with metastatic\u00a0disease. These patients usually receive\u00a0immunotherapy<\/a>, the harnessing of a patient’s own immune system, as the earliest form of\u00a0treatment. Immunotherapy\u00a0has revolutionized metastatic melanoma care.\u00a0Foth says the treatment is effective in about half of melanoma patients, sometimes with deep and durable responses.\u00a0<\/p>\n If immunotherapy fails or becomes less effective, physicians switch to targeted therapies as a secondary line of treatment. Targeted therapies\u00a0attack\u00a0oncoproteins and their effectors\u00a0to\u00a0kill cancer cells or\u00a0slow\u00a0their\u00a0growth.\u00a0<\/p>\n “Patients with other mutations like\u00a0BRAF\u00a0have access to clinically approved secondary\u00a0lines of treatment.\u00a0But\u00a0patients with\u00a0NRAS-driven melanoma do not have effective\u00a0targeted therapies to treat their cancer,” says McMahon. “Daraxonrasib\u00a0is a targeted therapy that may provide another path for treatment and hope for patients affected by this devastating disease.”\u00a0<\/p>\n The team also\u00a0observed\u00a0that some of the models became resistant to the drug, as often\u00a0happens in patients taking\u00a0pathway-targeted therapies. Resistance to\u00a0daraxonrasib\u00a0was\u00a0tied to mutations in the mitogen-activated protein kinase (MEK1),\u00a0a protein downstream of RAS,\u00a0or to loss of expression of cyclophilin A,\u00a0a\u00a0chaperone protein\u00a0required\u00a0for the\u00a0inhibitory action\u00a0of\u00a0daraxonrasib\u00a0toward RAS proteins.\u00a0<\/p>\n “We will need to do more research\u00a0to\u00a0find\u00a0drug combinations, based\u00a0on a backbone of\u00a0daraxonrasib, that will increase the depth and durability of melanoma patient responses,” says McMahon.\u00a0<\/p>\n McMahon\u00a0and Foth\u00a0hope the drug will move into a clinical trial for patients who are either ineligible for immunotherapy or\u00a0whose immunotherapy did not work.\u00a0<\/p>\n “This\u00a0research reflects the power of Huntsman Cancer Institute’s integrated approach, where laboratory discovery, translational research, and clinical trials come together to accelerate progress for patients,”\u00a0says\u00a0Neli Ulrich, PhD, MS,\u00a0executive director of the Comprehensive Cancer Center and\u00a0chief scientific\u00a0officer\u00a0at Huntsman Cancer Institute, Jon and Karen Huntsman Presidential Professor in Cancer\u00a0Research, and professor of population health sciences at the U.\u00a0“We are proud to contribute to advances that have the potential to change treatment options for our patients with melanoma. This is of utmost importance\u00a0in Utah and the Mountain West, where melanoma is\u00a0a very common\u00a0cancer.”\u00a0<\/p>\n The critical research happening every day at Huntsman Cancer Institute is supported by the National Institutes of Health\/National Cancer Institute, including Cancer Center Support Grant P30 CA042014, as well as Huntsman Cancer Foundation.\u00a0<\/p>\n Source:<\/p>\n Huntsman Cancer Institute at the University of Utah<\/a><\/p>\n Journal reference:<\/p>\n