Biochemical pharmacology of adenylyl cyclases in cancer

Bikash Chandra Jena; Daniel P Flaherty; Valerie P O'Brien; Val J Watts

doi:10.1016/j.bcp.2024.116160

Biochemical pharmacology of adenylyl cyclases in cancer

Biochem Pharmacol. 2024 Mar 24:116160. doi: 10.1016/j.bcp.2024.116160. Online ahead of print.

Authors

Bikash Chandra Jena¹, Daniel P Flaherty¹, Valerie P O'Brien², Val J Watts³

Affiliations

¹ Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
² Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA. Electronic address: vpobrien@purdue.edu.
³ Borch Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA. Electronic address: wattsv@purdue.edu.

PMID: 38522554
DOI: 10.1016/j.bcp.2024.116160

Abstract

Globally, despite extensive research and pharmacological advancement, cancer remains one of the most common causes of mortality. Understanding the signaling pathways involved in cancer progression is essential for the discovery of new drug targets. The adenylyl cyclase (AC) superfamily comprises glycoproteins that regulate intracellular signaling and convert ATP into cyclic AMP, an important second messenger. The present review highlights the involvement of ACs in cancer progression and suppression, broken down for each specific mammalian AC isoform. The precise mechanisms by which ACs contribute to cancer cell proliferation and invasion are not well understood and are variable among cancer types; however, AC overactivation, along with that of downstream regulators, presents a potential target for novel anticancer therapies. The expression patterns of ACs in numerous cancers are discussed. In addition, we highlight inhibitors of AC-related signaling that are currently under investigation, with a focus on possible anti-cancer strategies. Recent discoveries with small molecules regarding more direct modulation AC activity are also discussed in detail. A more comprehensive understanding of different components in AC-related signaling could potentially lead to the development of novel therapeutic strategies for personalized oncology and might enhance the efficacy of chemoimmunotherapy in the treatment of various cancers.

Keywords: Adenylyl Cyclase; Cancer; G protein; GPCR; Hallmarks of Cancer; cAMP signaling.

Publication types

Review