Abstract
Platinum drugs are heavily used first‐line chemotherapeutic agents for many solid tumours and have stimulated substantial interest in the biological activity of DNA‐binding metal complexes. These complexes generate DNA lesions which trigger the activation of DNA damage response (DDR) pathways that are essential to maintain genomic integrity. Cancer cells exploit this intrinsic DNA repair network to counteract many types of chemotherapies. Now, advances in the molecular biology of cancer has paved the way for the combination of DDR inhibitors such as poly (ADP‐ribose) polymerase (PARP) inhibitors (PARPi) and agents that induce high levels of DNA replication stress or single‐strand break damage for synergistic cancer cell killing. In this review, we summarise early‐stage, preclinical and clinical findings exploring platinum and emerging ruthenium anti‐cancer complexes alongside PARPi in combination therapy for cancer and also describe emerging work on the ability of ruthenium and gold complexes to directly inhibit PARP activity.
Highlights
Replication stress or single-strand break damage for synergistic cancer cell killing
PARP inhibitors (PARPi) are active in homologous recombination (HR)-deficient cancers, those lacking BRCA1/2, their utility is limited by the development of resistance which may occur through restoration of HR function.[135]
Further mechanistic investigations revealed that these ruthenium-PARPi conjugates have improved poly (ADP-ribose) polymerase (PARP) inhibitory activity compared to the free PARPi ligand and possess multi-targeting properties through DNA binding and transcription inhibition
Summary
Inhibiting DNA synthesis remains one of the central strategies in cancer therapy.[31]. Haslina Ahmad is a synthetic chemist who has been active in drug design, drug delivery and nanomaterial synthesis for almost 11 years. Chemistry (2009) from the University of Sheffield. She has started her academic position at the Universiti Putra Malaysia (2009), and currently an Associate Professor in Inorganic. Her research focus includes design, synthesis and drug delivery of metal-based compounds for cancer. She is the author of over 30 publications (citations: 318, H-index:12) and 60 conference presentations
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