Research pick: Screening for prostate cancer drugs - "Human caveolin-1 a potent inhibitor for prostate cancer therapy: a computational approach"

Researchers in India have taken a computational approach to investigate a protein that could become a novel target for new drugs to prostate cancer therapy. Uzma Khanam, Puniti Mathur, and Bhawna Rathi of Amity University and Balwant Kishan Malik of Sharda University, explain how the target, a protein known as caveolin-1, acts as a scaffold within certain types of cell membranes. The protein interacts with proteins involved in cell signalling and can regulate their activity.

Importantly, it was already known that caveolin-1 levels are elevated in the blood serum of men with prostate cancer. Indeed, this protein is secreted to promote blood vessel growth, angiogenesis, as well as cell proliferation. It also blocks the natural programmed cell death, apoptosis, which allows tumours to grow unfettered.

The team has used a computerized model of the protein to allow them to see how small molecules, putative pharmaceuticals, might fit into pockets in the protein, how they might “dock” with the protein, in other words. This kind of computer simulation of docking behaviour has wrought many novel drugs for a wide range of diseases in the past.

The team explains how they used molecular docking, structural base molecular modelling and molecular dynamics simulations to search for compounds that would inhibit the protein. They used a predictive model to screen against a large database of compounds. Their study has gleaned several potential lead compounds that dock with the active site of the protein. Blocking the protein might block its activity and prevent blood vessel growth and cell proliferation in a tumour within the prostate gland. The team suggests that the biochemical characteristics of these compounds with the protein should now be the focus of laboratory work in the search for new drugs to treat prostate cancer.

Khanam, U., Malik, B.K., Mathur, P. and Rathi, B. (2019) ‘Human caveolin-1 a potent inhibitor for prostate cancer therapy: a computational approach‘, Int. J. Computational Biology and Drug Design, Vol. 12, No. 3, pp.203-218.