Related Experiment Video

Updated: Jun 3, 2025

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
06:38

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

13.5K

Dynamics of resistance to immunotherapy and TKI in patients with advanced renal cell carcinoma

Matteo Santoni1, Veronica Mollica2, Alessandro Rizzo3

  • 1Medical Oncology Unit, Macerata Hospital, Macerata, Italy.

Cancer Treatment Reviews
|January 12, 2025
PubMed

Insights

Understanding resistance to first-line cancer immunotherapies is crucial. This review explores how cancer cells and their environment develop resistance to treatments like nivolumab and pembrolizumab, aiding the development of better strategies.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • First-line immune-based combinations are standard for metastatic renal cell carcinoma (mRCC), offering significant patient benefits.
  • However, primary resistance and disease progression remain critical challenges in mRCC treatment.
  • Understanding resistance mechanisms is vital for improving patient outcomes.

Purpose of the Study:

  • To review and explore the mechanisms of resistance to first-line immune-based combinations in metastatic renal cell carcinoma.
  • To identify biological patterns associated with resistance to immunotherapy and tyrosine kinase inhibitors.
  • To provide insights for developing strategies to overcome treatment resistance.

Main Methods:

  • Literature review of studies on resistance mechanisms in metastatic renal cell carcinoma.
  • Categorization of resistance mechanisms into intrinsic (cancer cell-related) and extrinsic (stromal or immune cell-related).
  • Detailed examination of resistance pathways for specific drugs including nivolumab, pembrolizumab, axitinib, cabozantinib, and lenvatinib.

Main Results:

  • Resistance to nivolumab and pembrolizumab can be intrinsic to cancer cells or extrinsic, involving stromal or immune cells.
  • Axitinib resistance is linked to increased Nuclear protein 1 (NUPR1) or decreased insulin receptor (INSR) expression.
  • Cabozantinib resistance may involve secretion of non-VEGF pro-angiogenic factors, while lenvatinib resistance can stem from pathway reactivation or alternative pathway activation (e.g., EGFR-PAK2-ERK).

Conclusions:

  • Identifying resistance mechanisms is key to overcoming them in metastatic renal cell carcinoma.
  • Understanding these mechanisms can guide the development of novel therapeutic strategies.
  • Overcoming resistance will improve treatment efficacy, duration of response, and overall patient outcomes in mRCC.
Keywords:
CabozantinibImmune-based combinationsLenvatinibNivolumabPembrolizumabRCCResistance

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