A recent study conducted by the American Association for the Advancement of Science e published in Science Translational Medicine highlighted a promising treatment for aggressive and transformed lung and prostate cancers. The drug in question, selinexor, has been successfully tested on mice, offering new perspectives in the field of oncological therapy. The research team identified a therapeutic target in a category of highly aggressive and lethal lung and prostate cancers, for which effective treatment options were limited.
The discovery also reveals that selinexoralready used and approved by Food and Drug Administration (FDA), for other pathologies, could sensitize these tumors to chemotherapy, reducing their plasticity, and thus opening up new treatment possibilities that could be rapidly re-proposed for clinical use. Neuroendocrine transformation is a process that some lung and prostate cancers undergo, often as a result of acquired resistance to targeted therapies. Once transformed, these tumors become highly resistant to conventional treatments, leading to low survival rates in patients.
Lung cancer
Interestingly, lung and prostate cancers that have undergone neuroendocrine transformation bear similarities to small cell lung cancers, which are also highly aggressive. Building on previous findings related to small cell lung cancers, which are dependent on the nuclear transporter exportin-1, the research team, led by Alvaro Quintanal-Villalonga of the American Association for the Advancement of Scienceinvestigated whether transformed neuroendocrine tumors possessed a similar vulnerability.
Prostate cancer
The research team found that, prior to transformation, lung and prostate cancers harbored high amounts of exportin-1, which the scientists linked to the inactivation of the tumor suppressor genes TP53 and RB1. As a result, the tumors were unusually sensitive to selinexor. Treatment with selinexor, in mice with early stage lung and prostate tumors, prevented neuroendocrine transformation and potentiated the anticancer effects of drugs approved anticancer drugs, come l’enzalutamide, against consolidated tumors transformed into neuroendocrine. “Safe exportin-1 inhibitors are already available in the clinic, which could facilitate the transposition of their approach for these difficult-to-treat malignancies”, declared the authors.
In conclusion, this research offers new perspectives in the fight against aggressive lung and prostate cancers, providing a possible combination of therapies to improve the effectiveness of existing treatments and enhance the chances of a cure for patients affected by these serious pathologies.