New molecular target could lead to cancer drugs with fewer side effects

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

New molecular target for cancer treatment

Researchers at Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) have discovered a new molecular drug target that could lead to new cancer drugs with fewer effects secondary.

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

For the first time, researchers have 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 growth and spread. of several diseases such as colon cancer. , endometriosis and ovarian hyperstimulation syndrome. Such growth of blood vessels is called angiogenesis. The team’s recent study was published in the Journal of Cell Sciences.

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

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

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

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

This study was supported by grants from the National Cancer Institute, the National Institutes of Health, and the US Department of Defense. Other co-authors of 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, the dopamine D2 receptor, on endothelial cells” by Chandrani Sarkar, Debanjan Chakroborty, Sandeep Goswami, Hao Fan, Xiaokui Mo and Sujit Basu, May 31 2022, Journal of Cell Sciences.
DOI: 10.1242/jcs.259617

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