Our Research

Clinical Success of Platinum Drugs and their Limitations

The serendipitous discovery by Barnett Rosenberg that cis-diamminedichloroplatinum(II), more commonly known as cisplatin, can inhibit the tumour growth heralded a new era of cancer research based on metallopharmaceuticals. To date, cisplatin and its analogues are some of the most effective chemotherapeutic agents in clinical use and are used against a variety of malignancies including, colorectal, lung, testicular and ovarian cancers. The anticancer properties of this simple inorganic compound are remarkable, particularly against testicular cancer.

Prior to the introduction of cisplatin, testicular cancer was a deadly disease for men with high mortality rates of approximately 70%. Platinum-based chemotherapy has dramatically reversed this trend, with curative rates exceeding 90% in early stage cases. Carboplatin is a second-generation platinum drug against a similar spectrum of cancers but with lower toxicities. Oxaliplatin was approved for clinical use as recently as 2003 and used in combination with 5-fluorouracil against advanced metastatic colorectal cancers.

Diagram of cisplatin, carboplatin and oxaliplatin
FDA-approved Platinum(II) Anticancer Drugs

The cytotoxic action of these compounds requires a combination of processes including cell entry, drug activation, DNA binding and cellular responses. Upon cell entry, the platinum drugs are activated by aquation and bind nuclear DNA. Formation of platinated DNA adducts lead to arrest of key cellular functions, such as transcription, and triggers a variety of cellular responses, such as repair. However, several challenges in the clinical application of these platinum-based chemotherapies remain, including their high toxicity, severe side-effects and incidence of drug resistance. Furthermore, despite the tremendous amounts of resources invested into developing new platinum drugs over the past few decades, but there have only been only few successes. These challenges have spurred renewed interest in uncovering new metallodrugs for cancer therapy.

Research Interests

Our research interest lies at the interface of chemistry and biology, in the study and development of metallocomplexes for targeted cancer therapy. Our work focuses mainly on Pt- and Ru-based complexes as non-classical therapeutic agents and elucidating their modes of action. We are also actively pursuing fluorescence probes that would allow us to investigate these compounds in live cell models. Our 4 broad areas of research are:

1) Developing the chemistry of platinum(IV) carboxylates as anticancer prodrug complexes

2) Fluorescence probes for the investigation of cisplatin and its parent platinum(IV) prodrug complexes

3) Metallocomplexes as Immuno-Chemotherapeutic agents

4) Coordination-directed 3-component Assembly of ruthenium-arene complexes for drug discovery