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Third row transition metals for the treatment of cancer.

ABSTRACT: Platinum compounds are a mainstay of cancer chemotherapy, with over 50% of patients receiving platinum. But there is a great need for improvement. Major features of the cisplatin mechanism of action involve cancer cell entry, formation mainly of intrastrand cross-links that bend and unwind nuclear DNA, transcription inhibition and induction of cell-death programmes while evading repair. Recently, we discovered that platinum cross-link formation is not essential for activity. Monofunctional Pt compounds such as phenanthriplatin, which make only a single bond to DNA nucleobases, can be far more active and effective against a range of tumour types. Without a cross-link-induced bend, monofunctional complexes can be accommodated in the major groove of DNA. Their biological mechanism of action is similar to that of cisplatin. These discoveries opened the door to a large family of heavy metal-based drug candidates, including those of Os and Re, as will be described.

SUBMITTER: Johnstone TC

PROVIDER: S-EPMC4342973 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Third row transition metals for the treatment of cancer.

Johnstone Timothy C TC Suntharalingam Kogularamanan K Lippard Stephen J SJ

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 20150301 2037

Platinum compounds are a mainstay of cancer chemotherapy, with over 50% of patients receiving platinum. But there is a great need for improvement. Major features of the cisplatin mechanism of action involve cancer cell entry, formation mainly of intrastrand cross-links that bend and unwind nuclear DNA, transcription inhibition and induction of cell-death programmes while evading repair. Recently, we discovered that platinum cross-link formation is not essential for activity. Monofunctional Pt co ...[more]

PMID: 25666060

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