Platinum-Based Combination Therapy: Molecular Rationale, Current Clinical Uses, and Future Perspectives

Abstract

Platinum drugs are common in chemotherapy, but their clinical applications have been limited due to drug resistance and severe toxic effects. The combination of platinum drugs with other drugs with different mechanisms of anticancer action, especially checkpoint inhibitors, is increasingly popular. This combination is the leading strategy to improve the therapeutic efficiency and minimize the side effects of platinum drugs. In this review, we focus on the mechanistic basis of the combinations of platinum-based drugs with other drugs to inspire the development of more promising platinum-based combination regimens in clinical trials as well as novel multitargeting platinum drugs overcoming drug resistance and toxicities resulting from current platinum drugs.

Anticancer Diiron Vinyliminium Complexes: A Structure–Activity Relationship Study

“…Indeed, this category of compounds offers peculiar properties associated with the presence of one or more transition elements, i.e., the availability of a variety of oxidation states, coordination environments and geometries, and the possibility of replacement and/or activation of ligands under suitable conditions [ 7 , 8 , 9 ]. Such arsenal of tools may provide an increased added pharmaceutical value with respect to common organic molecules, and in this light few platinum complexes have been successfully employed worldwide in clinical treatments against several types of tumors, in combination with other drugs [ 10 , 11 ]. On the other hand, the toxicity of the metal center may represent a serious issue, and this is certainly the case of platinum, a “heavy metal” belonging to the 5d series [ 12 , 13 ].…”

The Effect of Shenyi Capsule on Non-Small-Cell Lung Cancer Combined with Chemotherapy from the Yin-Yang Perspective

“…Platinum-based chemotherapy is currently the first-line treatment for advanced NSCLC [33]. Almost all platinum preparations have serious toxic side effects such as digestive reaction and bone marrow suppression [34]. Chemoresistance is a basic problem that limits the efficacy of many chemotherapy regimens [35].…”

“…Chemoresistance is a basic problem that limits the efficacy of many chemotherapy regimens [35]. In recent years, we 2 Evidence-Based Complementary and Alternative Medicine have tried to avoid toxic side effects and chemoresistance as much as possible through drug combination [34][35][36][37].…”

Prodrug-based nano-delivery strategy to improve the antitumor ability of carboplatin in vivo and in vitro

“…Among them, chemotherapy is still the mainstream method (Huang et al., 2019 ), so it is necessary to restrain the shortcomings of chemotherapy such as low therapeutic effect and multidrug resistance (Mangal et al., 2017 ; Zhao et al, 2017 ). Platinum-based drugs account for 80% of tumor treatment formulas (Rossi & Di Maio, 2016 ; Yu et al., 2020 ), and their therapeutic mechanism are closely concerned with the production of reactive oxygen species (ROS) (Ma et al., 2017 ) which is considered as a mediator of DNA damage (Srinivas et al., 2019 ) and a signal molecule in tumors (Moloney & Cotter, 2018 ; Carvalho et al., 2019 ). Though the low concentration of ROS can promote the proliferation, growth, and differentiation of tumor cells.…”