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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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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...
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Tumor Immunotherapy01:27

Tumor Immunotherapy

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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.
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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Drugs that Stabilize Microtubules01:15

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Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
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Cancer Therapies02:49

Cancer Therapies

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Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
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Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

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Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
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Related Experiment Video

Updated: Dec 21, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Antifibrotic therapy to normalize the tumor microenvironment.

Anette Hauge1, Einar K Rofstad2

  • 1Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Journal of Translational Medicine
|May 22, 2020
PubMed
Summary
This summary is machine-generated.

Targeting the fibrotic tumor microenvironment (TME) aims to improve cancer treatment. While some antifibrotic therapies show promise, like losartan for pancreatic cancer, understanding CAF heterogeneity is crucial for safe, effective strategies.

Keywords:
Antifibrotic therapyCancer-associated fibroblastsExtracellular matrixLosartanMicroenvironment normalizationProfibrotic signaling pathwaysTargeted treatmentsTumor microenvironment

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Area of Science:

  • Oncology
  • Cancer Biology
  • Fibrosis Research

Background:

  • Tumors often feature fibrotic regions within the tumor microenvironment (TME), characterized by fibroblasts, immune cells, extracellular matrix (ECM), and interstitial fluid.
  • An abundant fibrotic TME is linked to poor treatment outcomes in cancer patients.
  • Normalizing the TME is a hypothesized strategy to enhance cancer therapy effectiveness.

Purpose of the Study:

  • To review and categorize strategies for normalizing the fibrotic TME through targeted antifibrotic therapy.
  • To analyze the dual effects of antifibrotic therapies, which can either enhance or impede treatment outcomes.
  • To identify promising therapeutic avenues, such as targeting cancer-associated fibroblasts (CAFs) and their signaling pathways.

Main Methods:

  • Categorization of antifibrotic approaches into three main strategies: targeting ECM components, targeting CAFs, and targeting CAF-activating signaling pathways.
  • Review of agents used for each strategy, including ECM-degrading enzymes (collagenase, hyaluronidase), CAF-eliminating/reprogramming agents, and signaling pathway inhibitors (e.g., losartan targeting TGF-β).
  • Analysis of studies reporting conflicting outcomes of antifibrotic therapy, considering factors like CAF subpopulations and treatment parameters.

Main Results:

  • Antifibrotic therapy presents a "two-edged sword" with studies showing both enhanced treatment response and increased tumor growth/metastasis.
  • Conflicting results may stem from the heterogeneity of CAFs, with some promoting and others inhibiting tumor progression.
  • Factors such as disease stage, treatment duration, and induced immune cell recruitment influence antifibrotic therapy outcomes.

Conclusions:

  • Targeting the TGF-β signaling pathway, particularly with losartan, shows promise, with observed benefits in pancreatic cancer treatment.
  • Further research into the mechanisms of tumor fibrosis is essential for developing safe and effective antifibrotic treatments.
  • Understanding CAF heterogeneity is critical for optimizing antifibrotic strategies and improving cancer patient outcomes.