Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.

Cancer cells frequently develop resistance to chemotherapeutic therapies and targeted drugs, which has been a significant challenge in cancer management. With the growing advances in technologies in isolation and identification of natural products, the potential of natural products in combating cancer multidrug resistance has received substantial attention. Importantly, natural products can impact multiple targets, which can be valuable in overcoming drug resistance from different perspectives. In the current review, we will describe the well-established mechanisms underlying multidrug resistance, and introduce natural products that could target these multidrug resistant mechanisms. Specifically, we will discuss natural compounds such as curcumin, resveratrol, baicalein, chrysin and more, and their potential roles in combating multidrug resistance. This review article aims to provide a systematic summary of recent advances of natural products in combating cancer drug resistance, and will provide rationales for novel drug discovery.

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies are particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment of tumors affects CAR-T cells, limiting the treatment’s effectiveness and safety. Therefore, enhancing CAR-T cell infiltration capacity and resolving the immunosuppressive responses within the tumor microenvironment could boost the anti-tumor effect. Specific strategies include structurally altering CAR-T cells combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring the tumor microenvironment and the status of CAR-T cells is beneficial in further investigating the viability of such strategies and advancing CAR-T cell therapy.