Related Experiment Video
Updated: Jul 13, 2025
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Primary and acquired resistance to first-line therapy for clear cell renal cell carcinoma
Serena Astore1, Giulia Baciarello1, Linda Cerbone1
1Medical Oncology, San Camillo Forlanini Hospital, Rome 00152, Italy.
Abstract:
The introduction of first-line combinations had improved the outcomes for metastatic renal cell carcinoma (mRCC) compared to sunitinib. However, some patients either have inherent resistance or develop resistance as a result of the treatment. Depending on the kind of therapy employed, many factors underlie resistance to systemic therapy. Angiogenesis and the tumor immune microenvironment (TIME), nevertheless, are inextricably linked. Although angiogenesis and the manipulation of the tumor microenvironment are linked to hypoxia, which emerges as a hallmark of renal cell carcinoma (RCC) pathogenesis, it is only one of the potential elements involved in the distinctive intra- and inter-tumor heterogeneity of RCC that is still dynamic. We may be able to more correctly predict therapy response and comprehend the mechanisms underlying primary or acquired resistance by integrating tumor genetic and immunological markers. In order to provide tools for patient selection and to generate hypotheses for the development of new strategies to overcome resistance, we reviewed the most recent research on the mechanisms of primary and acquired resistance to immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) that target the vascular endothelial growth factor receptor (VEGFR).We can choose patients' treatments and cancer preventive strategies using an evolutionary approach thanks to the few evolutionary trajectories that characterize ccRCC.
Insights
First-line treatments improve metastatic renal cell carcinoma (mRCC) outcomes, but resistance is common. Integrating genetic and immune markers may predict response and overcome resistance to therapies like immune checkpoint inhibitors (ICIs) and VEGFR-targeted tyrosine kinase inhibitors (TKIs).
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Metastatic renal cell carcinoma (mRCC) treatment has advanced with first-line combinations, yet intrinsic or acquired resistance remains a challenge.
- Resistance mechanisms are multifactorial, involving angiogenesis, the tumor immune microenvironment (TIME), and hypoxia, all contributing to RCC's heterogeneity.
- Understanding these complex interactions is crucial for improving patient outcomes.
Purpose of the Study:
- To review current research on primary and acquired resistance mechanisms to immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) in mRCC.
- To explore the link between angiogenesis, TIME, and hypoxia in RCC pathogenesis and resistance.
- To identify potential biomarkers for predicting therapy response and developing strategies to overcome resistance.
Main Methods:
- Literature review of recent studies on resistance mechanisms to ICIs and TKIs in mRCC.
- Analysis of the interplay between angiogenesis, TIME, and hypoxia in RCC.
- Exploration of genetic and immunological markers for therapy response prediction.
Main Results:
- Resistance to mRCC therapies, including ICIs and VEGFR-targeted TKIs, is a significant clinical hurdle.
- Angiogenesis, TIME, and hypoxia are interconnected factors influencing RCC heterogeneity and treatment response.
- Integrating tumor genetic and immunological markers shows promise for predicting therapy response and understanding resistance.
Conclusions:
- Further research integrating genetic and immunological markers is needed to predict treatment response and overcome resistance in mRCC.
- An evolutionary approach to understanding ccRCC may aid in patient selection and treatment strategy development.
- Targeting resistance mechanisms is key to improving long-term outcomes for mRCC patients.
More Related Videos
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:40Cancer Stem Cells and Tumor Maintenance
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...