Hope for cancer patients, Punjabi University researchers find solution to enhance chemotherapy efficacy
A recent study conducted at Punjabi University has found solutions to make chemotherapy more effective in the treatment of cancer and reduce its side effects.
Under the supervision of Prof Om Silakari of the Department of Pharmaceutical Sciences and Drug Research of the university, Dr Baddipadige Raju, an ICMR Senior Research Fellow in MRP and Ph.D. Researcher, has conducted important research on understanding and resolving chemoresistance associated with a drug-metabolising enzyme (DME).
Dr Raju has published 24 international peer-reviewed research articles, including nine as the first author, in prestigious journals such as ACS Omega, RSC New Journal of Chemistry, International Journal of Biological Macromolecules, Molecular Diversity, Journal of Biomolecular Structure and Dynamics, and RSC Advances, and more than 130 scientists worldwide have cited this research in their research works.
Dr Raju is currently working as Project Scientist-II at the prestigious Institute of Life Sciences, Bhubaneswar, India.
Dr Raju said that he worked on P4501B1 (CYP1B1) to understand the nature of and solutions to problems associated with this enzyme.
He explained that this enzyme reduces the effect of the drugs docetaxel and paclitaxel, which are used in chemotherapy and are generally used for the treatment of breast, lung, and ovarian cancer.
Because of this, chemotherapy does not always prove to be very effective.
To solve this, it was necessary to find inhibitors to reduce the effect of this enzyme. He stated that through his research, he reached a solution through advanced CADD techniques, including machine learning, molecular docking, molecular dynamics simulations, 3-D-QSAR modeling, and free energy perturbation studies, followed by in vitro enzyme assay and cell cytotoxicity.
Through their experiments, they found that the drugs chlorprothixene, nadifloxacine, and ticagrelor are effective against this enzyme, resulting in increased positive effects of chemotherapy.
Prof Om Silakari said that chemoresistance, which reduces the effect of chemotherapy, remains a major global challenge, resulting in an insufficient availability of effective drugs to kill cancer cells and consequently causing cancer patients to die.
He stated that such enzymes often inactivate anti-cancer drugs, reduce their effectiveness, and lead to a drug resistance state where the drug does not work as intended.
To solve this situation, using these drugs in combination with such inhibitors as adjuvant therapy can prove effective. He explained that recognising the urgent need to solve this challenge, Dr Raju’s research focused on finding new solutions by targeting CYP1B1, which is involved in anti-cancer drug inactivation and resistance.
He said that although many anti-cancer drugs face such resistance, they specifically chose the drugs docetaxel and paclitaxel for this study. He added that during the research, network pharmacology studies were conducted to identify the enzymes responsible for the inactivation and resistance of these drugs.
A large amount of data was collected in this regard and analysed using online tools.
During the study, the drugs chlorprothixene, nadifloxacin, and ticagrelor, which can act as inhibitors, were identified. Giving these drugs as inhibitors as co-treatment with chemotherapy significantly increases the sensitivity of cancer cells to the drug, leading to better results.
He mentioned that an important advantage of using the discovered inhibitors is that these are already clinically approved drugs and there is no safety risk. He noted that this is preliminary research in this direction. After testing it on humans or animals on a large scale, its great benefits can be realized for all of humanity.
Vice Chancellor Dr Jagdeep Singh congratulated the researcher and his supervisor for this quality research and expressed his appreciation.
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