Related Experiment Video

Updated: Jan 10, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

11.1K

Tumor microenvironment-driven drug resistance in urologic cancers: mechanisms and therapeutic targets

Gi-Eun Yang1,2, Seo-Yeong Yoon1,2, Ju-Seog Lee3

  • 1Department of Biomedical Science, Dong-A University, Busan, 49315, Korea.

Genes & Genomics
|November 26, 2025
PubMed

Insights

Therapeutic resistance in urologic cancers is driven by the tumor microenvironment (TME). Targeting TME components offers new strategies to improve treatment outcomes for renal cell carcinoma, bladder cancer, and prostate cancer.

Area of Science:

  • Urologic Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Therapeutic resistance is a significant obstacle in treating renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PCa).
  • The tumor microenvironment (TME) critically influences treatment failure for therapies like androgen deprivation therapy (ADT), VEGF inhibitors, and immune checkpoint inhibitors (ICIs).

Purpose of the Study:

  • To review how specific TME components contribute to therapeutic resistance in urologic cancers.
  • To explore novel strategies and technologies for overcoming TME-driven resistance.

Main Methods:

  • Literature review of studies investigating TME components and therapeutic resistance.
  • Analysis of mechanisms by which cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), immunosuppressive cells, and hypoxia promote resistance.
  • Examination of emerging therapeutic strategies and advanced technologies for TME modulation.

Main Results:

  • CAFs, ECM stiffening, immunosuppressive cells, and hypoxia promote resistance by driving oncogenic reactivation, epithelial-mesenchymal transition (EMT), hindering immune infiltration, and fostering cancer stemness.
  • Hypoxia and metabolic reprogramming activate HIF-2α, leading to lactate accumulation and TME acidification, further promoting resistance.
  • Promising strategies include combination therapies (ICIs with anti-angiogenics or TGF-β inhibitors), ECM-modulating agents, and hypoxia-targeted drugs.

Conclusions:

  • Understanding and targeting TME-driven resistance mechanisms is crucial for improving urologic cancer treatment.
  • Novel approaches like single-cell transcriptomics, spatial transcriptomics, organoid co-cultures, and TME biomarkers are vital for patient stratification and therapeutic development.
  • Integrating TME biology into clinical practice is essential to overcome resistance and enhance patient outcomes.
Keywords:
Cancer-associated fibroblasts (CAFs)Combination therapyImmune evasionTherapeutic resistanceTumor microenvironment (TME)Urologic cancers

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.9K
Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis09:28

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis

Published on: May 12, 2019

10.7K

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
5.9K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.7K