New Molecular Target Could Result in Cancer Drugs With Fewer Side Effects

Researchers found that unlike the currently available anti-VEGF-A anti-angiogenic agents, the new selective dopamine D2 receptor agonists are inexpensive and have well-established and manageable side effects.

New Molecular Target for Cancer Treatment

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) researchers have discovered a new molecular drug target that might lead to new cancer medicines with fewer side effects.

Previous research has shown that vascular endothelial growth factor-A (VEGF-A) – a powerful cytokine (signaling protein) – and dopamine (a neurotransmitter/neurohormone) play critical roles in a variety of physiological and pathological functions. Dr. Sujit Basu and colleagues performed further preclinical analysis of VEGF-A as a target for the development of novel cancer therapy approaches in a new laboratory study.

For the first time, the researchers discovered that VEGF-A can increase the expression of dopamine D2 receptors on endothelial cells, which can then be stimulated to stop the growth of blood vessels, which fuel the growth and spread of several diseases such as colon cancer, endometriosis, and ovarian hyperstimulation syndrome. Such blood vessel growth is called angiogenesis. The team’s recent study was published in the Journal of Cell Science.

“This is a very compelling discovery that opens up new pathways for developing effective new anti-angiogenic therapy for the treatment of cancer and other diseases where VEGF-A is a known driver of disease growth and spread,” said Basu, who also serves as a professor at The Ohio State University College of Medicine and is a member of the Translational Therapeutics Program at the OSUCCC – James.

Basu notes that, unlike the presently available anti-VEGF-A anti-angiogenic agents, selective dopamine D2 receptor agonists are inexpensive and have well-established and manageable side effects.

“These drugs are devoid of the serious side effects of the currently used anti-VEGF-A anti-angiogenic agents in the clinics. We believe they merit further investigation as a viable treatment approach in cancer and other diseases driven by the VEGF-A pathway,” Basu said.

Researchers expect to begin testing these drugs through clinical trials in the near future.

This study was funded by grants from the National Cancer Institute, National Institutes of Health, and the U.S. Department of Defense. Additional coauthors in this study include Chandrani Sarkar, Debanjan Chakroborty, Sandeep Goswami, Hao Fan, and Xiaokui Mo.

Reference: “VEGF-A controls the expression of its regulator of angiogenic functions, dopamine D2 receptor, on endothelial cells” by Chandrani Sarkar, Debanjan Chakroborty, Sandeep Goswami, Hao Fan, Xiaokui Mo and Sujit Basu, 31 May 2022, Journal of Cell Science.
DOI: 10.1242/jcs.259617

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