Related Experiment Video

Updated: Apr 15, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

941

The RAF-MEK-ERK pathway: targeting ERK to overcome obstacles to effective cancer therapy

Zutao Yu1, Shiqi Ye, Gaoyun Hu

  • 1Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, 410013, Changsha, Hunan, China.

Future Medicinal Chemistry
|April 1, 2015
PubMed
Abstract

Insights

Acquired resistance to BRAF and MEK inhibitors in cancer therapy is a major challenge. Targeting ERK1/2, a key component of the RAF-MEK-ERK pathway, may overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • RAF-MEK-ERK pathway inhibitors show initial efficacy in cancer treatment.
  • Acquired drug resistance develops in most patients after 6-8 months, limiting clinical benefit.

Purpose of the Study:

  • To elucidate mechanisms of acquired resistance to BRAF and MEK inhibitors.
  • To identify optimal therapeutic targets for overcoming acquired resistance in the RAF-MEK-ERK pathway.

Main Methods:

  • Review of current literature on BRAF, MEK, and ERK inhibitors.
  • Analysis of the role of ERK1/2 in cancer signaling and drug resistance.

Main Results:

  • Mechanisms of acquired resistance to BRAF and MEK inhibitors have been identified.
  • ERK1/2 plays a critical role, activating numerous substrates and participating in feedback loops.
  • ERK1/2 exhibits unique characteristics, including specific catalysis by MEK and absence of acquired resistance mutations.

Conclusions:

  • ERK1/2 is a crucial node in the RAF-MEK-ERK pathway.
  • ERK1/2's unique properties make it a promising target.
  • Targeting ERK1/2 may represent an effective strategy to overcome acquired resistance to RAF-MEK-ERK pathway inhibitors.

More Related Videos

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods07:49

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

6.6K
Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.4K

Related Concept Videos

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...
8.5K
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...
9.5K
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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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...
9.2K
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...
8.0K