PILOT PROJECT - RSK Inhibition as a Targeted Therapy for Basal-Like Breast Cancer Pilot Project

$112,807U54FY2025CANIH

Tennessee State University, Nashville TN

Investigators

Margaret M Whalencontact Quincy Antoine Quick

Linked publications & trials

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Abstract

There is an ongoing need for targeted therapies for the treatment of basal-like breast cancer (BLBC), the major form of triple-negative breast cancer (TNBC). The Serine/Threonine protein kinase family, RSK, is a family of downstream MEK1/2-ERK1/2 effectors active in the majority of BLBCs and is proposed to act as a driver of metastatic breast cancer. Based on this hypothesis, a phase 1/1b clinical trial using the first-in-human pan RSK inhibitor, PMD-026, is underway. Based on encouraging results, an expansion of the clinical trial is planned, but this increased accrual raises the concern, as RSK function in the tumor immune response is controversial. Furthermore, the RSK1/2 forms are associated with transformation and metastasis, whereas RSK3/4 are implicated as tumor suppressors, and therefore, a pan RSK inhibitor may not be the best therapeutic approach. A possible alternative to PMD-026 is the specific RSK1/2 inhibitor, C5â-n-propyl cyclitol SL0101 (1b).

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