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Commentary Open Access
Volume 5 | Issue 2 | DOI: https://doi.org/10.33696/Signaling.5.112

Teaching an Old Drug a New Trick: Targeting Treatment Resistance in Genitourinary Cancers

  • 1Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, 1410 Laney Walker Blvd., 30912, USA
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Corresponding Author

Vinata B. Lokeshwar, vlokeshwar@augusta.edu

Received Date: February 03, 2024

Accepted Date: March 19, 2024

Abstract

In the quest for improving the clinical outcome of patients with metastatic genitourinary cancers, including metastatic renal cell carcinoma (mRCC), the emphasis often is on finding new targeted therapies. However, two studies by Jordan et al. (Oncogenesis 2020) and Wang et al. (Cancer Cell Int 2022) demonstrate the feasibility of improving the efficacy of a modestly effective drug Sorafenib against mRCC by attacking a mechanism hijacked by RCC cells for inactivating Sorafenib. The studies also identified hyaluronic acid synthase -3 (HAS3) as a bonafide target of Sorafenib in RCC cells. The studies demonstrate that an over-the-counter drug Hymecromone (4-methylumbelliferone) blocks inactivation of Sorafenib in RCC cells and improves its efficacy against mRCC through the inhibition of HAS3 expression and HA signaling. In the broader context, improving the efficacy of “old and failed drugs” that have favorable safety profiles should increase the availability of effective treatments for patients with advanced cancers.

Keywords

HAS3, Hyaluronic acid, UGT-1A9, Hymecromone/4-methylumbelliferone, Genitourinary cancer, Sorafenib

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