Samir Parekh, MD, associate professor, Icahn School of Medicine, Mount Sinai Health System, discusses a promising potential biomarker for response to selinexor in patients with myeloma.

Selinexor has been tested in patients with various types of cancer, Parekh says, and the overall response rate across all the cancers it has been tested in is about 20%. It seems as though these patients have a molecular characteristic that allow them to respond to this novel drug for an extended period of time, he says, and investigators from Mount Sinai Health System have been working to determine what distinguishes the patients that respond for long period of time from those who don’t.

In a study presented at the 2018 ASH Annual Meeting, patients treated with selinexor were divided into 2 groups: patients with >3 months of response and patients with < 3 months of response. By taking the tumor cells, extracting the RNA and sequencing it, investigators were able determine differences between these 2 groups. Patients with a shorter progression-free survival had a higher level of a protein that is crucial to cell cycle called E2F1, which seems to be associated with resistance to selinexor. These findings need to be confirmed in larger studies, Parekh concludes, but E2F1 can potentially be an important biomarker that can help physicians identify which patients will have better outcomes with the agent.

Videos

Dr. Parekh on Potential Biomarker for Novel Drug in Myeloma

Samir Parekh, MD, associate professor of Medicine, Mount Sinai Health System, discusses the mechanism of action of selinexor in multiple myeloma.

Selinexor is an oral selective inhibitor of nuclear export (SINE). The drug has been tested in phase I/II trials and is currently under review by the FDA. In November 2018, the FDA granted a priority review designation to a new drug application for the inhibitor as a treatment for patients with penta-refractory multiple myeloma. 

The drug has a unique mechanism of action in that it blocks a transporter called XPO1, says Parekh. The transporter is responsible for shuttling cargo proteins and messenger RNA between the nucleus and the cytoplasm. By blocking the export of these molecules, selinexor enables key changes in the dynamic that is responsible for tumor growth and suppression. Specifically, an increase in tumor suppressor proteins such as p53 and a reduction in oncogenic proteins within the NF-κBpathway are very important for myeloma growth. When selinexor is introduced, however, it essentially “shuts off” the cancerous cells and causes them to die, he says.

Samir Parekh, MD

Articles

Dr. Parekh on Potential Biomarker for Novel Drug in Myeloma

Dr. Parekh on the Mechanism of Action of Selinexor in Myeloma