Review of Cisplatin and Oxaliplatin in Current Immunogenic and Monoclonal Antibodies Perspective

Abstract

Platinum-based chemotherapy made a paradigm shift in the treatment of different cancers initially; however, the success of these agents may have reached the peak as researchers have tried different combination regimes in different trials without having major differences in the end results. New frontiers of research were opened up firstly with this discovery that conventional chemo-radiation therapy can induce immunological cell death by recruiting high-mobility group box 1 (HMGB1) protein which triggers the T cell immunity and secondly monoclonal antibodies agents which were regrettably not effective as “monotherapy”; however, the combination with conventional chemotherapy had demonstrated good results. Different monoclonal antibodies and conventional chemotherapeutic combination regimes are currently in use and researchers are trying different other combinations as well to glean the maximum benefits from them. Several strategies conferring resistance to platinum compounds have been identified, but there is still significant research required to achieve full understanding of these resistance mechanisms to overcome the ineffectiveness or toxicities of platinum compounds. It seems reasonable in the current perspective when conventional chemotherapeutic agents exhibited immunogenic cell death and they are currently in use with monoclonal antibodies to revisit the platinum agent’s pharmacology. This may discover new basis for combination chemotherapy with monoclonal antibodies which may improve the current cancer treatments by opening new vistas for newer combination regimes with less toxicity and better efficacy. In this article we review the pharmacologies of both cisplatin and oxaliplatin in the drug development perspectives and explore the possible association of these drugs with monoclonal antibodies.

Chemical Imaging of Platinum-Based Drugs and their Metabolites

“…Oxaliplatin can be non-enzymatically converted by reaction with water and chloride to [Pt(DACH)Cl 2 ], [Pt(DACH)Cl(OH)], and [Pt(DACH)(OH) 2 ]29. Pt(ΙΙ) drugs are known to form adducts with nucleobases resulting in DNA cross-links30, which inhibits DNA synthesis and repair, which eventually leads to apoptosis, or programmed cell death. Pt compounds also have a high affinity towards sulfur-containing molecules.…”

Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview

“…These have been proven to be effective strategies to treat malignancies [ 86 , 87 , 88 ]. Cisplatin and oxaliplatin are known bifunctional alkylators that react with adjacent guanine residues creating inter or intra-strand crosslinks, interfering with DNA replication or transcription, and contributing to cell death [ 89 ]. Various analogs of these drugs were tested in vitro.…”

The p38 MAPK Signaling Activation in Colorectal Cancer upon Therapeutic Treatments

“…Oxaliplatin was the first drug from the diaminocyclo-hexane platinum family to be successfully developed in the clinic and is recommended as first-line chemotherapeutic agent. The most accredited mechanisms for oxaliplatin-induced anti-tumor effects include the ability to create cross-links and generate single and double-strand breaks in DNA, the ability to inhibit DNA and mRNA synthesis, and the ability to induce immunogenic cell death [30]. Nevertheless, oxaliplatin application in CRC as a monotherapy is restricted because of the occurrence of high toxicity caused by the high therapeutic doses and the development of drug resistance [31].…”