Metallodrugs in Targeted Cancer Therapeutics: Aiming at Chemoresistance-related Patterns and Immunosuppressive Tumor Networks

Tumor cell chemoresistance is a major challenge in cancer therapeutics. Major select metal-based drugs are potent anticancer mediators yet they exhibit adverse sideeffects and are efficient against limited types of malignancies. A need, therefore, arises for novel metallodrugs with improved efficacy and decreased toxicity. Enhancement of antitumor drugs based on anticancer metals is currently a very active research field, with considerable efforts having been made toward elucidating the mechanisms of immune action of complex metalloforms and optimizing their immunoregulatory bioactivity through appropriate synthetic structural modification(s) and encapsulation in suitable nanocarriers, thereby enhancing their selectivity, specificity, stability, and bioactivity. In that respect, comprehending the molecular factors involved in drug resistance and immune response may help us develop new approaches toward more promising chemotherapies, reducing the rate of relapse and overcoming chemoresistance. In this review, a) molecular immunerelated mechanisms in the tumor microenvironment, responsible for lower drug sensitivity and tumor relapse, along with b) strategies for reversing drug resistance and targeting immunosuppressive tumor networks, while concurrently optimizing the design of complex metalloforms bearing anti-tumor activity, are discussed in an effort to identify and overcome chemoresistance mechanisms for effective tumor immunotherapeutic approaches.