The role of the MET/AXL pathway as a new target for multikinase inhibitors in renal cell carcinoma

ABSTRACT

Introduction: The management of patients with metastatic renal cell carcinoma has drastically changed in recent years thanks to the development of new drugs directed against essential targets involved in tumour growth and metastasis. Our improved understanding of disease-related altered pathways has allowed this revolution, which is still progressing. Despite these improvements, prognosis of patients with metastatic renal cell carcinoma remains poor, making the discovery of new targets essential.

Areas covered: Angiogenesis and mTOR (mammalian target of rapamycin) inhibitors are active treatments for patients with metastatic renal cell carcinoma but cancer cells inexorably develop several strategies that allow them to escape the inhibition carried out by these agents. MET and AXL pathway dysregulation appear to be important components related to tumour progression, metastasis and resistance to angiogenesis inhibitors. Clinical activity of MET inhibitors has been tested in small and large clinical trials with the achievement of surprising results that will probably change the course of this disease in the future.

Expert commentary: Over the last few years several drugs have been developed for the management of metastatic renal cell carcinoma leading to a complex scenario. Indeed, no predictive factors have been included in clinical practice for the identification of patients more likely to benefit from a specific treatment and so in the coming years our efforts will probably be focused on this issue. Moreover, a better selection of patients could help the development of new agents targeting specific altered pathways of the disease through the planning of clinical trials tailored for specific subpopulations of patients unlikely to respond to standard therapy.

KEYWORDS:

• Metastatic renal cell carcinoma
• cabozantinib
• precision medicine
• personalized medicine
• targeted therapy
• MET
• AXL
• TKI
• mTOR
• PD-1
• PD-L1

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This article was not funded.