Advances in Renal Cell Carcinoma Drug Resistance Models

Abstract

Renal cell carcinoma (RCC) is the most common form of kidney cancer. Systemic therapy is the preferred method to eliminate residual cancer cells after surgery and prolong the survival of patients with inoperable RCC. A variety of molecular targeted and immunological therapies have been developed to improve the survival rate and prognosis of RCC patients based on their chemotherapy-resistant properties. However, owing to tumor heterogeneity and drug resistance, targeted and immunological therapies lack complete and durable anti-tumor responses; therefore, understanding the mechanisms of systemic therapy resistance and improving clinical curative effects in the treatment of RCC remain challenging. In vitro models with traditional RCC cell lines or primary cell culture, as well as in vivo models with cell or patient-derived xenografts, are used to explore the drug resistance mechanisms of RCC and screen new targeted therapeutic drugs. Here, we review the established methods and applications of in vivo and in vitro RCC drug resistance models, with the aim of improving our understanding of its resistance mechanisms, increasing the efficacy of combination medications, and providing a theoretical foundation for the development and application of new drugs, drug screening, and treatment guidelines for RCC patients.

Identification of Prognostic and Predictive Biomarkers and Druggable Targets among 205 Antioxidant Genes in 21 Different Tumor Types via Data-Mining

“…This indicates that these tumor entities may be more suitable for chemosensitization via inhibition of antioxidant genes than the other tumor types investigated. Interestingly, these tumor types are known to be rather chemoresistant [ 73 , 74 , 75 , 76 , 77 , 78 ]. Hence, chemosensitization strategies may be attractive to improve treatment outcomes.…”

“…Renal clear cell carcinoma is not usually treated with cytotoxic chemotherapy because of its ineffectiveness. Surgery, immunotherapy, and targeted therapy with tyrosine kinase inhibitors are applied with modest success [ 73 , 74 , 79 ]. The situation in renal papillary cell carcinoma is not fundamentally different [ 75 , 80 ].…”

Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma

“…By contrast, acquired resistance arises when cancer cells initially respond to TKI treatment but eventually relapse as the drug loses efficacy over time due to the acquisition of various resistance mechanisms. Multiple in vitro and in vivo models involving cell lines, patient-derived xenografts (PDX), organoids, and genetically engineered mouse models (GEMMs) have been developed to assess the mechanisms, dynamics, and progression of drug resistance [ 28 ] . These models help elucidate the complex interplay between cancer cells and their microenvironment, offering valuable information for developing strategies to overcome resistance and improve treatment outcomes.…”

The emerging role of long non-coding RNAs in renal cell carcinoma progression and clinical therapy via targeting metabolic regulation

“…However, due to tumor heterogeneity and drug resistance, immunotherapy lacks a complete anti-tumor response. In the course of clinical treatment, about 30% of RCC patients have metastasis at the time of diagnosis, and 30%–70% of RCC patients are still likely to relapse after surgical treatment ( Xiang et al, 2022 ). As a result, it is essential to better understand RCC pathogenesis and progression-related mechanisms to search for the new strategies for the treatment of this fatal malignancy.…”