Renal cell carcinoma (RCC) is one of the most lethal urologic malignancies.
Partial or radical nephrectomy is the major surgical management for localized RCC, however,
almost 30% of patients will develop recurrence and metastasis after surgery. Metastatic
RCC (mRCC) is a disease with a very poor prognosis, and the 5-year survival of
the mRCC is commonly less than 10%. Unfortunately, mRCC is highly resistant to chemo
and radiotherapy. Therefore, mRCC treatment has become a big challenge for researchers
as well as clinicians. RCC is characterized as clear genetic background, especially
with von Hippel-Lindau (VHL) gene loss or mutation in more than 70% of the cases.
Several molecular factors and signaling pathways have been discovered to possess impact
on the progression of RCC, including VHL-HIF-VEGF angiogenesis signaling,
PI3K/AKT/mTOR signaling, epithelial-to-mesenchymal transition-related pathways, and
Wnt/β-catenin pathway, which play crucial roles in the growth, invasiveness, metastasis
and angiogenesis of RCC. Based on the recent studies of these signaling pathways, some
medicines as well as immune check-point inhibitors have been developed, which have
shown potential therapeutic effects for mRCC. Therefore, our current review aims to summarize
the recent progress of the treatment for mRCC, with a special focus on the strategies
to improve the responsiveness of medicines in patients with mRCC.