Researchers at UT Southwestern Medical Center have discovered a vulnerability in treatment-resistant lung cancer and found that the drug Selinexor may be an effective treatment. According to Science Daily, the study describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for the treatment of other types of cancer.
Dr Michael A. White, author of the study, assembled multiple research teams and used robotic machines to create and sift through trays with thousands of cancel cell/potential drug combinations to uncover the weakness of the KRAS mutation. The KRAS oncogene is believed to be responsible for about 25% of all lung cancer cases.
The scientists found that targeting and inactivating the protein XPO1, found in the cell nucleus and used to transport gene products from the nucleus to the cytoplasm, killed most of the KRAS mutant cancer cells, according to Science Daily. Dr Pier Scaglioni explains, “We found that inhibiting the XPO1 gene kills lung cancer cells that are dependent on KRAS. The unexpected coincidence here is that there is an existing drug that will inhibit XPO1.”
White adds, “We know that this drug hits the XPO1 target in people. But we will not know whether the drug will be effective until clinical trials are done, which should be completed in about two years.” Based on the results of this study, Selinexor will be the focus of a multicenter lung cancer clinical trial led by Dr David Gerber of UT Southwestern, which is expected to open for enrollment next year.
In preclinical results from cancer cells and mouse models in the study, 83% of the KRAS mutant lung cancers responded to Selinexor. The study found the remaining 17% of lung cancers could be killed by adding a second drug to inhibit YAP1, a gene known to be involved in the promotion of several other cancers, reports Science Daily. The drug Verteporfin appeared to be effective in blocking YAP1, which is currently used to treat blood vessel disorders in the eye.
Source: Science Daily