Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Video

Updated: Feb 14, 2026

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.7K

Targeting the MAPK Pathway in RAS Mutant Cancers.

Sarah G Hymowitz1, Shiva Malek2

  • 1Department of Structural Biology, Genentech Inc., South San Francisco, California 94080.

Cold Spring Harbor Perspectives in Medicine
|February 15, 2018
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

The Ras Gene02:38

The Ras Gene

7.4K
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
7.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

8.6K
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...
8.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

9.0K
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...
9.0K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

5.5K
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:
5.5K
C4 Pathway and CAM01:27

C4 Pathway and CAM

49.4K
Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
49.4K
Other Glycolytic Pathways01:24

Other Glycolytic Pathways

1.0K
The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
1.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Biomarker analysis from patients with metastatic PDAC treated with TGFβ antibody, NIS793, plus abraxane+gemcitabine vs. abraxane+gemcitabine alone in a phase II, open label, randomized study.

Clinical cancer research : an official journal of the American Association for Cancer Research·2026
Same author

Dynamic transitioning between MAPK-driven and WNT-driven cell states drives intestinal cancer and shapes therapy response.

Nature genetics·2026
Same author

Filling a nick in NIK: Extending the half-life of a NIK inhibitor through structure-based drug design.

Bioorganic & medicinal chemistry letters·2023
Same author

Ternary complex dissociation kinetics contribute to mutant-selective EGFR degradation.

Cell chemical biology·2023
Same author

Structural basis for SHOC2 modulation of RAS signalling.

Nature·2022
Same author

CRAF dimerization with ARAF regulates KRAS-driven tumor growth.

Cell reports·2022

Targeting KRAS mutant cancers remains challenging. This review explores inhibiting mitogen-activated protein kinase (MAPK) signaling with specific kinase inhibitors to treat these tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • KRAS mutant cancers lack targeted therapies despite extensive drug discovery.
  • Mitogen-activated protein kinase (MAPK) signaling is crucial in KRAS-driven tumorigenesis.

Purpose of the Study:

  • To review challenges and opportunities in targeting KRAS mutant tumors.
  • To explore the use of conformation-specific kinase inhibitors targeting MAPK signaling.

Main Methods:

  • Structural analysis of BRAF and MEK inhibitors.
  • Mechanistic studies of MAPK signaling components.
  • Investigating kinase-dependent and -independent functions.

Main Results:

  • Insights into how MAPK signaling regulates KRAS-driven tumorigenesis.

More Related Videos

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System
08:54

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System

Published on: March 20, 2016

10.3K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K

Related Experiment Videos

Last Updated: Feb 14, 2026

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.7K
Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System
08:54

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System

Published on: March 20, 2016

10.3K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K
  • Understanding the role of kinase and non-kinase functions in tumor growth.
  • Identifying strategies for small molecule kinase inhibitor development.

    • Conclusions:

    • Targeting MAPK signaling offers a promising therapeutic strategy for KRAS mutant cancers.
    • Conformation-specific kinase inhibitors show potential for treating RAS mutant tumors.
    • Further research into MAPK signaling pathways can lead to novel cancer treatments.