Researchers identify drugs to overcome chemotherapy resistance
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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