Resistance management of axitinib/axitinib

Axitinib/Axitinib is a targeted therapy drug mainly used to treat advanced renal cell carcinoma (RCC). Although it has shown good efficacy in clinical applications, drug resistance problems have gradually emerged and become a major challenge in the treatment process. The resistance mechanism of axitinib is complex and involves multiple biological pathways and molecular mechanisms.

Tumor cells develop drug resistance through genetic mutations or epigenetic changes. For example, mutations in the VHL gene may reduce the sensitivity of tumor cells to hypoxic signals, thereby affecting the activation of the VEGF pathway. In addition, mutations or overexpression of other related receptors, such as PDGFR and FGFR, may also help tumor cells escape the inhibitory effect of axitinib. These changes allow tumor cells to survive and continue to proliferate under the influence of axitinib.

Changes in the tumor microenvironment can also promote the development of drug resistance. Tumor cells change the surrounding microenvironment by secreting pro-angiogenic factors, cytokines and matrix components, thereby improving their own viability and adaptability. This enhanced adaptability enables tumor cells to rapidly adjust their metabolism and growth patterns under pressure from targeted drugs, leading to the development of drug resistance.

Treatment strategies for axitinib resistance mainly include combination therapy and drug substitution. The combined use of immune checkpoint inhibitors, such as PD-1/PD-L1 antibodies, can enhance the body's immune response and overcome tumor resistance to axitinib. In addition, targeted drugs targeting different resistance mechanisms, such as FGFR inhibitors, can also be considered for use in combination with axitinib to achieve better therapeutic effects.

In short, the treatment of axitinib resistance needs to comprehensively consider the molecular characteristics of the tumor and microenvironmental factors, and adopt a combination of multiple strategies in order to improve the prognosis and quality of life of patients.

Reference materials:https://www.nature.com/articles/cddis2014125