Related Experiment Video

Updated: Aug 26, 2025

Assaying Protein Kinase Activity with Radiolabeled ATP
08:05

Assaying Protein Kinase Activity with Radiolabeled ATP

Published on: May 26, 2017

18.5K

Targeting Extracellular Signal-Regulated Protein Kinase 1/2 (ERK1/2) in Cancer: An Update on Pharmacological

Leilei Fu1, Siwei Chen1, Gu He2

  • 1Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.

Journal of Medicinal Chemistry
|October 7, 2022
PubMed

Insights

Selective inhibition of Extracellular signal-regulated protein kinase 1/2 (ERK1/2) offers a promising cancer therapy strategy. Targeting ERK1/2 can overcome resistance to upstream inhibitors and improve therapeutic efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The RAS-RAF-MEK-ERK (MAPK) pathway is crucial in cancer, with abnormal activation linked to poor prognosis.
  • Existing inhibitors targeting RAS, RAF, and MEK show promise but face acquired resistance, limiting efficacy.
  • Mutations in upstream components like RAS, RAF, and MEK can lead to resistance against current therapies.

Purpose of the Study:

  • To review the oncogenic roles of ERK1/2 in cancer.
  • To summarize the signaling network involving ERK1/2.
  • To discuss single- and dual-target ERK1/2 inhibitors in preclinical and clinical development.

Main Methods:

  • Literature review of oncogenic roles of ERK1/2.
  • Analysis of the MAPK signaling pathway network.
  • Compilation of data on ERK1/2 inhibitors from preclinical and clinical trials.

Main Results:

  • ERK1/2, the sole substrate of MEK1/2, plays a significant role in cancer progression.
  • Selective ERK1/2 inhibition presents a strategy to bypass upstream resistance mechanisms.
  • Various single- and dual-target ERK1/2 inhibitors are under investigation.

Conclusions:

  • Targeting ERK1/2 directly is a viable strategy to overcome acquired resistance in cancer therapy.
  • Further development of ERK1/2 inhibitors holds potential for improved cancer therapeutics.
  • Selective ERK1/2 inhibition offers a new avenue for effective cancer treatment.

More Related Videos

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

7.5K
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.3K

Related Concept Videos

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
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
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
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...
3.8K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.7K
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