Novel Strategies to Enhance the Activity of Platinum Drugs Against Colorectal Cancer

Aoife M. McKeon
2019
Colorectal cancer represents a major rapidly growing global challenge and a disease that warrants the need for extensive research into it's prevention, diagnosis and treatment. Late stage colorectal cancer is typically treated with surgery and adjuvant chemotherapy. The FOLFOX chemotherapeutic regimen which comprises the Ptbased drug oxaliplatin is the current gold standard worldwide. However, despite the undisputed success of Pt-based chemotherapeutics, deleterious side effects and drug
more » ... cts and drug resistance are the ever present major obstacles to effective colorectal cancer treatment. Thus, there remains a constant need to develop novel therapeutic strategies. In an effort to circumvent the mechanisms that give rise to drug resistance, and to mitigate other undesired side-effects, thousands of Pt based compounds have been developed to date that conform to and deviate from the classical cis-PtA2X2 structure of clinically approved Pt drugs. Lloyd Kelland in his Nature Reviews Cancer article titled "The resurgence of platinum-based cancer chemotherapy" stated that "four major strategies can now be proposed to circumvent platinum-drug resistance in cancer patients: first, new, improved platinum drugs; second, improved delivery of platinum to tumours; third, co-administration of platinum drugs with pharmacological modulators of resistance mechanisms; and fourth, combining platinum drugs with new molecularly targeted drugs". Chapter 1 provides an introduction into the role of Pt-based drugs as anticancer agents, including 'classical' Pt drugs that are currently in use in the clinic, and a number of unconventional compounds currently under development. The remainder of Chapter 1 is split into three parts where part I reviews the function of heat shock proteins and highlights their role in cancer progression and survival, part II considers the role of cell penetrating peptides and how they can be exploited for use in cancer treatment, and part III details the hedgehog signaling pathway and it's role in colorectal cancer developme [...]
doi:10.25419/rcsi.10802021.v1 fatcat:lxbpfuvdgjeqxjrt5me2cj2yim