Treatment strategies for clear cell renal cell carcinoma: Past, present and future

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, which is prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy. The burden it places on human health due to its refractory nature and rising incidence rate is substantial. Researchers have recently determined the ccRCC risk factors and optimized the clinical therapy based on the disease's underlying molecular mechanisms. In this paper, we review the established clinical therapies and novel potential therapeutic approaches for ccRCC, and we support the importance of investigating novel therapeutic options in the context of combining established therapies as a research hotspot, with the goal of providing diversified therapeutic options that promise to address the issue of drug resistance, with a view to the early realization of precision medicine and individualized treatment.

Keywords: clear cell renal cell carcinoma; cytokine; immune checkpoint inhibitor; immunological substance modification; obesity paradox; renal cancer stem cells; tyrosine kinase inhibitor.

Figure 1

Standard methods for the treatment of mccRCC. Cytokine therapy, targeted drug therapy, and ICI therapy are the standard mccRCC treatment options that have emerged successively in clinical history.

Figure 2

Molecular characteristics of ccRCC. VHL, PBRM1, BAP1, and SETD2 are all located in a region on the short arm of human chromosome 3. This region’s structural and functional deletion is known as “chromosome 3p loss”. Chromosome 3p loss has been confirmed as a common and carcinogenic driving event in ccRCC.

Figure 3

New strategies in clinical trials. (i) new targeted drugs; (ii) HAR immunotherapy; (iii) emerging drugs in combination with classic drugs.

Figure 4

New strategies in laboratory trials. (i) combining computer technology with basic experiments to uncover new molecular targets of ccRCC; (ii) eliminating abnormal lipid deposition in ccRCC cells, thereby inhibiting tumorigenesis and progression; (iii) improving the ability to identify and kill renal CSCs; (iv) continuing to focus on the immune system to lift immunosuppression and “stepping on the gas”.