A Review of the Mechanisms of Tumor Drug Resistance and Clinical Strategies

Abstract

Cancer treatment is a core challenge in clinical oncology. Despite the continuous advancement of chemotherapy, targeted therapy, and immunotherapy, the emergence of tumor drug resistance remains a key factor leading to treatment failure and worsening patient prognosis. Clinical data indicate that approximately 90% of treatment failures in patients with advanced cancer are directly related to drug resistance. Therefore, systematically analyzing the mechanisms of drug resistance and developing targeted strategies to address them are crucial for improving the efficacy of cancer treatment. This article systematically expounds on the main mechanisms of tumor drug resistance from the perspectives of tumor cell biological characteristics, tumor microenvironment regulation, and epigenetic modifications. These include reduced intracellular drug accumulation, mutations or aberrant expression of drug targets, inactivation of apoptotic pathways, cancer stem cell (CSC)-mediated resistance, and the regulatory role of immunosuppressive cells and cytokines in the tumor microenvironment. Furthermore, based on clinical practice, this article summarizes currently used strategies, such as drug development targeting resistance-associated molecules, chemotherapy regimen optimization and combination therapy, synergistic application of immunotherapy and conventional therapies, personalized treatment plan development, and the clinical translation of resistance monitoring technologies. Research has shown that the development of tumor drug resistance is the result of multiple factors and pathways, and a single strategy is unlikely to effectively reverse drug resistance. However, multi-target, multi-modal combination therapy based on resistance mechanisms, combined with dynamic resistance monitoring technology, can significantly improve treatment outcomes for patients with drug-resistant tumors. This article aims to provide a theoretical basis for clinicians to formulate tumor treatment plans and to guide future research related to drug resistance.