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Treatment of KRAS-Variant Cancers with Serotonin Transporter Inhibitors
Yale University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• The KRAS variant impacts responses to various cancer therapies. Ovarian tumors with the KRAS variant are resistant to treatment with standard chemotherapies including cisplatin.
• EOC tumors harboring the KRAS-variant were found to be significantly more resistant to treatment with platinum than those without the KRAS-variant. There is currently no drug available to specifically treat KRA-variant ovarian cancer.
• The method comprising administering to the subject an effective amount of a serotonin uptake inhibitor, wherein the subject comprises rs6176430 variant of the KRAS gene.
• The serotonin uptake inhibitor is more effective in killing a cancer cell comprising the rs61764340 variant of the KRAS gene than killing a corresponding cancer cell that doe not comprise the rs61764370 variant of the KRAS gene.
• The serotonin uptake inhibitor is more effective in inhibiting survival of a cancer cell comprising the re61764340 variant of the KRAS gene than in inhibiting survival of a corresponding cancer cell that does not comprise the rs61764970 variant of the KRAS gene.
• The administration of the serotonin uptake inhibitor results in inhibition of the growth of a tumor of the cancer.
WO2021236498A1
