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Related Concept Videos

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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Inhibition of Cdk Activity02:34

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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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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Enzyme-linked Receptors01:00

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Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

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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.
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Mitogens and the Cell Cycle02:38

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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Related Experiment Video

Updated: Oct 30, 2025

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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TRK Inhibitors: Tissue-Agnostic Anti-Cancer Drugs.

Sun-Young Han1

  • 1Research Institute of Pharmaceutical Sciences and College of Pharmacy, Gyeongsang National University, Jinju-si 52828, Korea.

Pharmaceuticals (Basel, Switzerland)
|July 2, 2021
PubMed
Summary

Larotrectinib and entrectinib, tropomyosin receptor kinase (Trk) inhibitors, target Trk fusions across cancer types. Tissue-agnostic development accelerated their approval and companion diagnostics.

Keywords:
NTRKTrkTrk fusionentrectiniblarotrectinibtissue-agnostic

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Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Tropomyosin receptor kinase (Trk) fusions are key drivers in various cancers.
  • Larotrectinib and entrectinib are approved Trk inhibitors offering a new treatment paradigm.

Purpose of the Study:

  • To review the development of larotrectinib and entrectinib.
  • To discuss other Trk inhibitors in clinical trials.
  • To highlight the impact of tissue-agnostic development and companion diagnostics.

Main Methods:

  • Review of clinical trial data for larotrectinib and entrectinib.
  • Analysis of tissue-agnostic development strategies.
  • Discussion of next-generation sequencing-based companion diagnostics.

Main Results:

  • Tissue-agnostic development expedited Trk inhibitor approvals.
  • Next-generation sequencing companion diagnostics enable Trk fusion detection.
  • On-target effects include central nervous system adverse events.

Conclusions:

  • Tissue-agnostic development is an effective strategy for targeted cancer therapies.
  • Companion diagnostics are crucial for identifying patients eligible for Trk inhibitors.
  • Further research into Trk inhibitors and their side effects is warranted.