Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview

Related Experiment Video

Updated: Sep 2, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
07:49

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

Published on: July 17, 2019

6.1K

Eunus S Ali1, Shamima Akter2, Sarker Ramproshad3

  • 1College of Medicine and Public Health, Flinders University, Bedford Park, 5042, Australia.

Cancer Cell International
|August 8, 2022
PubMed

Insights

The MAPK pathway is crucial in cancer, but inhibitors activate resistance. Novel combinatorial treatments targeting compensatory pathways are needed for better cancer therapy response.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Pharmacology

Background:

  • The mitogen-activated protein kinase (MAPK) or extracellular-signal-regulated kinase (ERK) pathway is vital for signal transduction.
  • Dysregulation of MAPK signaling due to genetic/epigenetic changes is implicated in various diseases, notably cancer.
  • While MAPK's role in homeostasis and pathology is studied, its regulation and action models require further preclinical and clinical investigation.

Purpose of the Study:

  • To investigate the complex MAPK signaling pathway in cancer treatment response.
  • To understand compensatory pathway activation and feedback loops induced by MAPK inhibition.
  • To explore natural bioactive products that modulate the MAPK pathway for cancer therapy.

Main Methods:

  • Review of current literature on MAPK signaling in cancer.
  • Analysis of compensatory mechanisms activated by MAPK inhibitors.
  • Exploration of plant, microbial, and marine-derived compounds targeting the MAPK pathway.

Main Results:

  • MAPK pathway alterations are common in cancer, affecting treatment response.
  • MAPK inhibitors often trigger resistance via compensatory feedback loops in tumor cells and the microenvironment.
  • Natural products with specific chemical structures show potential for modulating MAPK signaling.

Conclusions:

  • Targeting the MAPK pathway is critical for cancer treatment, but resistance mechanisms must be addressed.
  • Innovative combinatorial therapies are necessary to overcome resistance and improve cancer management.
  • Translational research incorporating natural bioactive products could lead to novel therapeutics targeting the MAPK pathway.
Keywords:
CancerChemopreventionChemoresistanceMAPK (ERK)Molecular mechanismsNatural bioactive compoundsRas oncogenesRas signaling

More Related Videos

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3.1K
Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells09:20

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

Published on: July 6, 2021

2.5K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

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...
6.4K
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...
7.8K
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
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
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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:
4.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K