Related Experiment Video

Updated: Aug 31, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

1.6K

Sensitivity towards HDAC inhibition is associated with RTK/MAPK pathway activation in gastric cancer

Therese Seidlitz1, Tim Schmäche1,2,3,4, Fernando Garcίa5

  • 1Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

EMBO Molecular Medicine
|August 22, 2022
PubMed

Insights

Researchers developed three gastric cancer organoid models to study pathway alterations. They discovered a new treatment approach targeting the RTK/MAPK pathway, showing promise for gastric adenocarcinoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Gastric cancer is a leading cause of death globally, driven by complex signaling pathway alterations.
  • Understanding these pathways is crucial for developing effective targeted therapies.
  • Existing model systems may not fully capture the heterogeneity of gastric cancer.

Purpose of the Study:

  • To create and characterize novel murine organoid models representing key gastric cancer signaling pathways.
  • To investigate the impact of specific pathway alterations on organoid phenotype, proteome, and drug sensitivity.
  • To identify novel therapeutic vulnerabilities in gastric cancer, particularly related to RTK/MAPK signaling.

Main Methods:

  • Generation of three distinct murine organoid models with defined genetic alterations (RAS-activated, WNT-activated, diffuse).
  • Morphological, phenotypic, and proteomic characterization of the organoid models.
  • Assessment of differential drug sensitivities and pathway dependencies, including RTK/MAPK interference and HDAC inhibition.
  • Validation of findings in patient-derived gastric adenocarcinoma organoids.

Main Results:

  • The three organoid models exhibited distinct morphological and proteomic profiles, reflecting their genetic backgrounds.
  • A differential sensitivity to RTK/MAPK pathway inhibition was observed, dependent on specific oncogenic drivers.
  • An association between RTK/MAPK pathway activity and susceptibility to histone deacetylase (HDAC) inhibition was identified.
  • This association was successfully validated in patient-derived organoids, suggesting a new therapeutic strategy.

Conclusions:

  • Murine organoid models provide valuable systems for studying gastric cancer heterogeneity and pathway interactions.
  • Targeting the RTK/MAPK pathway, in conjunction with HDAC inhibition, represents a potential novel treatment approach for specific gastric cancer subtypes.
  • Further research and clinical validation are warranted to translate these findings into patient care.
Keywords:
HDACiMAPKgastric cancerorganoids

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.3K
Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

6.6K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.9K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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...
6.6K