Related Experiment Video

Updated: May 21, 2025

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
13:56

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions

Published on: July 18, 2013

11.1K

Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response

Mary Helen Barcellos-Hoff1, Sue S Yom2

  • 1Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA. maryhelen.barcellos-hoff@ucsf.edu.

Nature Reviews. Cancer
|May 19, 2025
PubMed

Insights

Transforming growth factor-β (TGFβ) paradoxically suppresses healthy tissues but promotes established cancers. Targeting TGFβ

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The transforming growth factor-β (TGFβ) paradox describes its dual role in cancer: suppression in healthy tissues and promotion in established malignancies.
  • TGFβ inhibitors have shown limited success in clinical trials due to a lack of patient selection criteria.
  • Understanding TGFβ's role in DNA repair is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To explore the therapeutic potential of targeting TGFβ regulation of DNA repair in human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC).
  • To review how loss of TGFβ signaling impacts DNA repair and its potential for synthetic lethality induction.
  • To investigate TGFβ's role in predicting response to immune checkpoint inhibitors and the utility of biomarkers for patient selection.

Main Methods:

  • Review of existing literature on TGFβ signaling, DNA repair mechanisms, and HPV-driven HNSCC.
  • Analysis of the interplay between HPV, TGFβ inhibition, and DNA damage repair pathways.
  • Exploration of synthetic lethality strategies targeting DNA repair deficits.
  • Assessment of TGFβ's predictive value for immune checkpoint inhibitor response.

Main Results:

  • HPV inhibits TGFβ signaling, leading to reduced DNA damage repair in HNSCC.
  • This DNA repair deficit confers sensitivity to cancer treatments and contributes to favorable prognosis in HPV-positive HNSCC.
  • Targeting the DNA repair deficit caused by TGFβ loss offers a potential synthetic lethality strategy.
  • TGFβ pathway status may predict response to immune checkpoint inhibitors.

Conclusions:

  • TGFβ's complex role in cancer necessitates refined therapeutic strategies.
  • Targeting DNA repair deficits induced by TGFβ pathway alterations presents a promising approach for specific cancer types.
  • Biomarkers are essential for identifying patients who would benefit from TGFβ-targeted therapies, including immune checkpoint inhibitors.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.7K
Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter06:59

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Published on: March 31, 2022

2.4K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Proofreading01:43

Proofreading

Overview
53.7K
DNA Helicases00:55

DNA Helicases

DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
21.0K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
3.9K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.7K