Karyopharm Therapeutics (KPTI) Announces Publication of Strong Preclinical Data on Selinexor in NSCLC
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Karyopharm Therapeutics Inc. (Nasdaq: KPTI) announced that preclinical data describing XPO1 inhibition with selinexor (KPT-330), the Company’s lead, oral Selective Inhibitor of Nuclear Export / SINE™ compound, in a KRAS-mutant non-small cell lung cancer (NSCLC) model, were published online in Nature. The paper, titled, “XPO1 Dependent Nuclear Export is a Druggable Vulnerability in KRAS-mutant Lung Cancer,” discusses preclinical results supporting selinexor’s potential as a new therapeutic strategy for patients with highly aggressive and difficult to treat KRAS-mutant NSCLC.
In the manuscript, scientists from the University of Texas Southwestern Medical Center and Karyopharm demonstrated that KRAS-mutant NSCLC cells are addicted to Exportin 1 (XPO1) and that inhibition with selinexor induced robust cellular apoptosis of these malignant cells, both in vitro and in vivo.
“We are honored to collaborate with Dr. Michael White at UT Southwestern Medical Center on this important research. The KRAS gene is known to play an important role in cell division, differentiation and apoptosis,” said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. “This research provides an improved understanding of the role of XPO1 nuclear transport in KRAS-mutant NSCLC and recognizes the potential for therapeutic intervention utilizing an XPO1 inhibitor such as selinexor in certain patient sub-types that can be identified through genomic screening. Beyond NSCLC, these findings could have implications in other KRAS-driven malignancies, including in patients with KRAS mutant colorectal cancer.”
“Many of the most lethal human cancers harbor oncogenic mutant KRAS proteins, and this observation, combined with new detection methods to identify somatic KRAS mutant alleles in patient samples, has led to intensive efforts to develop drugs that inhibit KRAS activity,” said Erkan Baloglu, PhD, Senior Director, Discovery and Early Development Program Lead at Karyopharm, and co-author of the paper. “However, advances have been hindered by several factors, including druggability of key pathway members and the swift development of acquired-drug resistance to otherwise effective targeted therapies. These data show the dependence of KRAS-mutant NSCLC cells on XPO1-mediated nuclear export, suggesting that XPO1 inhibition could provide a promising new therapeutic strategy for a considerable cohort of patients with lung cancer when coupled with genomics-guided patient selection and observation.”
“Very importantly, this study also reveals potential predictive markers of response to selinexor and XPO1 inhibition,” said Yosef Landesman, PhD, Senior Director, Head of Scientific Affairs at Karyopharm and co-lead author of the paper. “Those markers are genes from two central cellular pathways: The NFκB pathway that controls inflammation and tumorigenesis, along with the Hippo signaling pathway that controls organ size, cell proliferation and apoptosis.”
As a result of this research, Karyopharm Therapeutics is evaluating the potential for a clinical trial of selinexor in patients with KRAS mutant NSCLC.
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