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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 are of three kinds RI, RII, and RIII. The RI...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...

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Related Experiment Video

Updated: Jun 25, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

From M7824 to SHR-1701: lessons for dual PD-L1/TGF-β targeting.

Ming Yi1,2, Tianye Li3, Kongming Wu4

  • 1Department of Breast Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Journal for Immunotherapy of Cancer
|June 23, 2026
PubMed
Summary

Retlirafusp alfa is a new bifunctional antibody approved for gastric cancer. Its approval highlights the importance of understanding how dual PD-L1 and TGF-β targeting works in specific patient groups.

Keywords:
AntibodyImmune Checkpoint InhibitorSolid tumorTumor microenvironment - TME

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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

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Last Updated: Jun 25, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Area of Science:

  • Immunotherapy
  • Gastrointestinal Oncology
  • Translational Medicine

Background:

  • Dual targeting of PD-L1 and TGF-β aims to overcome tumor immune evasion.
  • Previous agents like bintrafusp alfa showed inconsistent efficacy, prompting investigation into underlying mechanisms.
  • Tumor microenvironment factors, including stromal niches, influence response to dual immunomodulatory agents.

Purpose of the Study:

  • To analyze the implications of retlirafusp alfa's approval for gastric cancer treatment.
  • To explore the reasons for variable efficacy of dual PD-L1/TGF-β inhibitors.
  • To support biomarker-driven development strategies for novel immunotherapies.

Main Methods:

  • Review of clinical trial data and preclinical research on retlirafusp alfa and related agents.
  • Analysis of tumor microenvironment characteristics, including immune suppression and exclusion.
  • Pharmacodynamic assessment of dual-target engagement and downstream signaling.

Main Results:

  • Retlirafusp alfa (SHR-1701) approved in China for first-line treatment of PD-L1-positive advanced gastric/gastroesophageal junction adenocarcinoma.
  • TGF-β-mediated immune suppression and exclusion are spatially organized and context-dependent.
  • PD-L1 expression alone does not guarantee efficacy; other barriers may dominate.

Conclusions:

  • Retlirafusp alfa's approval validates dual PD-L1/TGF-β targeting in a selected patient population.
  • Understanding the tumor microenvironment is crucial for optimizing dual-targeting immunotherapy.
  • Future development should focus on biomarker selection, rational combinations, and pharmacodynamic validation.