Pazopanib/pazopanib belongs to the first generation of targeted therapy drugs

Pazopanib is a second-generation multi-target tyrosine kinase inhibitor (TKI) mainly used to treat advanced renal cell carcinoma (RCC) and soft tissue sarcoma (STS). The development of targeted therapy drugs has experienced continuous evolution from the first to the fourth generation. The improvements in each generation are aimed at improving efficacy, reducing side effects and overcoming drug resistance.

The first generationTKI mainly targets a single target, such as imatinib (Imatinib), which mainly acts on BCR-ABL and c-KIT, and is mainly used for chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Although these drugs are highly effective, patients are prone to develop drug resistance as treatment time prolongs.

As a second-generation TKI, pazopanib is a multi-target inhibitor. Compared with the first-generation, it not only inhibits VEGFR, but also inhibits multiple receptor tyrosine kinases such as PDGFR, FGFR and c-KIT, thereby blocking tumor angiogenesis and reducing the supply of nutrients required for tumor growth. This multi-target mode of action makes pazopanib still effective against more drug-resistant cancer types, especially in the treatment of advanced renal cell carcinoma and soft tissue sarcoma, showing good clinical efficacy.

In contrast, third-generation TKIs such as axitinib have further optimized their targeting effects and improved their selectivity for VEGFR, thus reducing side effects on other non-targets. The latest fourth-generation TKIs are beginning to be combined with immunotherapy, such as the new generation of VEGFR-TKIs combined with PD-1 inhibitors, which is becoming a new trend in the treatment of renal cancer.

Pazopanib’s mechanism of action makes it a first- or second-line treatment option for renal cell carcinoma and soft tissue sarcoma. Clinical studies have shown that pazopanib can significantly prolong progression-free survival (PFS) in patients with untreated metastatic renal cancer. Compared with first-generation TKIs, such as sorafenib, pazopanib has relatively controllable side effects, such as a lower incidence of hand-foot syndrome, and is better tolerated by patients. Therefore, it is widely used in clinical practice and recommended in treatment guidelines as a first-line option for advanced renal cancer.

Reference materials:https://www.votrient.com/