Cathepsin D inhibitors as potential therapeutics for breast cancer treatment against triple-negative and triple-positive breast cancers
Yogeeswari Perumal1, 2,
1Department of Pharmacy, Birla Institute of Technology and Science-Pilani-Hyderabad campus, Shameerpet, R.R. District, Hyderabad-500078, Telangana, India; 2Co-Founder, Yogee’s Bioinnovations Private Limited, Room No. 5, Technology Business Incubator, Birla Institute of Technology and Science-Pilani-Hyderabad campus, Shameerpet, R.R. District, Hyderabad-500078, Telangana, India
Breast cancer is the MOST COMMON CANCER in women all over India and accounts for 25% to 31% of all cancers in women globally. Approximately 15% of all breast cancers are diagnosed as triple negative breast cancer (TNBC)- an aggressive subtype. Currently TNBC has no treatment option except chemotherapy and surgery.
In our recent study, we have identified a therapeutic target, a lysosomal protease expressed not only in ER/PR positive, HER negative cell lines, but also in triple negative breast cancer cell lines. Drug candidates were designed and developed as a Cathepsin D (CatD) enzyme inhibitors, and were checked for anti-cancer activity and their role in inhibiting angiogenesis. Current status of research on Cathepsin D is vigorous to develop more specific and potent drug molecules in treating breast cancers in women. In spite of many other drug molecules and therapies available in the field of breast cancer and Oncology, latest clinical findings depict the need to develop targeted inhibition of genes/mediators involved in the downstream regulation of tumor progression and metastasis. On the other hand, the tumor cells are gaining resistance to drug molecules and taking another pathway in tumor progression. This is quite challenging to explore the new strategies involved for effective treatment of cancer.
The invented compounds (YS-1 and YS-12) from our laboratory have shown significant inhibitory activity towards CatD and also in reducing the growth of a panel breast cancer cells which included ER/PR positive with HER negative cell lines and triple negative breast cancer cell lines. Patent process has been initiated as these chemical compounds were novel. Further the candidate drugs exhibited antiangiogenic properties tested in-vivo in a zebra fish model.