Mysore/Mysuru: The laboratory of Dr. Basappa, Faculty at the Department of Studies in Organic Chemistry and also a Deputy Registrar-Administration, University of Mysore (UoM), has developed new breast cancer drug-like compounds.

Breast cancer, the most common occurring cancer in women and the second most common cancer overall, has resulted in a number of deaths worldwide. Breast cancer has reached 10 million while the number of people diagnosed with the dreaded disease has crossed the 19 million mark, experts have revealed. The current methods of treatment in use are Surgery (Mastectomy), Chemotherapy, Radiation and Hormonal Therapy.

In early 2018, Olaparib, sold under the brand name Lynparza, was approved by the Food and Drug Administration (FDA) for the first treatment of patients with advanced breast cancer, who had inherited mutations in the breast cancer type 1 and 2 susceptibility proteins (BRCA1&2) as a class of drugs known as PARP (poly(ADP-ribose) polymerase) inhibitors. The BRCA-1 and BRCA-2 genes give tumour suppressor proteins that help repair damaged DNA in cells.

However, both pre-clinical studies and clinical data demonstrate either intrinsic resistance to PARP inhibition or the development of acquired resistance to PARP inhibitors resulting in limitation of the clinical response to the currently approved PARP inhibitors. Therefore, the discovery of new PARP inhibitors is currently in need to treat advanced breast cancer patients. 

Dr. Basappa’s lab discovered oxadiazole-based PARP inhibitor, which has inhibited the viability of human breast cancer cells with an IC50 value of 1.4 micromolar when compared to Olaparib (3.2 micromolar). The laboratory experimental data in collaboration with Prof. Peter E. Lobie, Tsinghua Berkeley Shenzhen Institute, China, revealed that the newly discovered (5u) PARP inhibitor may serve as exemplars for the development of new therapeutics in breast cancer. This work has been accepted in the ‘Molecules’ MDPI Journal.

At present, Dr. Basappa’s lab is dedicated to commercialise two international patents, which he had designed, synthesised, characterised and studied in vitro, in vivo pharmacological effects of drug-like compounds that target trefoil factor 3 (PCT/WO/2018/226155) and Bcl2 antagonist of cell death (PCT/SG2018/050194). Recently, Indian Patent Office has granted a Patent on Bcl2 antagonist of cell death application (Patent No. 385095, Date of Grant. 24 December 2021).

Last week, Dr. Basappa received an e-mail from Mauro Piacentini, Editor-in-Chief of Nature Cell Death & Disease Journal, that  an article titled “Trefoil factor 3 promotes pancreatic carcinoma progression via WNT pathway activation mediated by enhanced WNT ligand expression” has been accepted, allowing him to be narrowed in taking these drug-candidates for clinical trials.

This work was partly supported by Centre of Excellence in Science, Engineering and Medicine, Vision Group on Science and Technology, Government of Karnataka.

Dr. Basappa is a student of former UoM VC Prof. K.S. Rangappa, CSIR Professor-Emeritus at the University, who is also involved in this discovery.

Dr. Basappa’s lab has published around 145 research papers in national and international peer-reviewed journals which include Proceedings of National Academy of Sciences, USA, Nature Scientific Reports, Journal of Biological Chemistry, Royal Society of Chemistry, American Chemical Society and Oxford Journals.