Rama Suntharalingam

Metallopharmaceuticals for the treatment of cancer 

Research Summary

Cancer stem cells (CSCs) are a distinct population of tumour cells that have the ability to self-renew, differentiate, and form metastatic tumours. CSCs effectively evade conventional chemotherapy and radiotherapy as these treatments specifically target fast growing cancer cells, and CSCs, due to their stem cell-like properties, divide more slowly. After surviving treatment, CSCs are able to regenerate the original tumour and/or produce invasive cancer cells that are able to colonise distant organs. For these reasons, CSCs are widely thought to be responsible for cancer relapse. Therefore, to provide a durable response and prevent tumour recurrence, chemotherapeutics must have the ability to remove the entire population of cancer cells, including CSCs. Therapeutic strategies capable of selectively killing CSCs and disrupting the microenvironments (niches) supporting these cells are the focus of several research programmes. Potential CSC therapeutic targets such as cell surface markers and various deregulated signalling pathways have been identified, but there is still no clinically approved drug that specifically kills CSCs. Many academia- and pharmaceutical-led studies aimed at developing chemical or biological anti-CSC agents are ongoing. Our group aims to harness the diversity and versatility offered by metals to develop inorganic compounds capable of potently and selectively killing CSCs (over bulk cancer cells and normal non-proliferating cells).

More generally, our group aims to use the structural, optical, redox, magnetic, and catalytic diversity offered by metal-containing small molecules to design and develop new generations of metallopharmaceuticals for the treatment of cancer as well as other diseases. The group also focuses on engineering new nano-material systems to deliver therapeutics to their site(s) of action.

Key Publications:

• Feld C, Johnson, A, Xiao Z, Suntharalingam K  (2020) Breast cancer stem cell potency of nickel(II)-polypyridyl complexes containing non-steroidal anti-inflammatory drugs Chemistry Europe Journal  10
• Eskandari A, Kundu A, Ghosh S, Suntharalingam K. (2019) A Triangular Platinum(II) Multinuclear Complex with Cytotoxicity Towards Breast Cancer Stem Cells. Angew Chem Int Ed Engl. 58(35):12059-12064.
• Suntharalingam K, et al. (2018) “A Copper(II)-Phenanthroline Metallopeptide that Targets and Disrupts Mitochondrial Function in Breast Cancer Stem Cells” Angew. Chem. 57, 287.
• Suntharalingam K, et al. (2018) “Highly charged, cytotoxic, cyclometalated iridium(III) complexes as cancer stem cell mitochondriotropics” Chem. Eur. J., 24 (57), 15205.
• Suntharalingam K, et al. (2016) “Breast Cancer Stem Cell Potent Copper(II)–Non-Steroidal Anti-Inflammatory Drug Complexes” Angew. Chem. 55, 2845.