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.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update

“…The treatment choice for patients who progress after adjuvant treatment will depend on the timing of their progression and their IMDC risk. Disease progression within six months may indicate drug resistance (Yang et al 2023 ). When patients with metastatic ccRCC progress within six months after adjuvant treatment with pembrolizumab, the panel recommends the TKI cabozantinib as the first-line treatment for intermediate-risk (consensus; LE: 5; GR: D) and poor-risk (recommendation; LE: 5; GR: D) patients.…”

Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies

“…According to a study from the European Prospective Investigation into Cancer and Nutrition (EPIC), a higher BMI is associated with a RR equal to 2.25 of RCC. The vitamin D and omega-3 trial (VITAL) study showed that a 5 Kg weight gain increases the risk by 25% in males and 35% in females [ 26 , 54 ]. Another study demonstrated that obesity represents a risk factor for ccRCC (RR = 1.8) and chRCC (RR = 2.2), while it is not associated with the development of pRCC [ 55 ].…”

“…CN is a controversial issue, as it has been shown that sunitinib—in combination with CN—was not superior to sunitinib alone, and therefore, requires further studies. For elderly patients with poor physical condition, tumor ablation is the most promising method because it has the advantage of being minimally invasive and requiring a short treatment time [ 54 ]. Instead, the metastatic ccRCC is treated with immunotherapy using interleukin 2 (IL-2) or interferon-α (IFN-α), which has remained the main treatment for more than 20 years, although response rates range from 15 to 25%.…”

The role of RNA-modifying proteins in renal cell carcinoma

“…Early-stage RCC is managed through nephrectomy, while advanced stages require systemic therapies such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) [ 17 ]. Recently, the combination of cabozantinib, a TKI, and the ICIs nivolumab and ipilimumab significantly increased the progression-free survival of advanced ccRCC patients compared with patients treated with nivolumab and ipilimumab [ 18 ].…”