Related Experiment Video

Updated: Jan 23, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

364

Dual Targeting of Autophagy and MEK in KRAS Mutant Cancer

Hongyun Zhao1, Bin Zheng1

  • 1Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Trends in Cancer
|June 19, 2019
PubMed

Insights

Inhibiting MEK-ERK signaling in KRAS-mutated cancers triggers autophagy. Blocking autophagy with chloroquine (CQ) or hydroxychloroquine (HCQ) boosts MEK-ERK inhibitor effectiveness in preclinical cancer models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • RAS-pathway signaling is crucial in cancer development.
  • MEK-ERK pathway inhibition is a strategy for KRAS-mutated cancers.
  • Autophagic flux is a cellular adaptation mechanism.

Purpose of the Study:

  • To investigate the role of autophagy in response to MEK-ERK inhibition in KRAS-mutated cancers.
  • To evaluate the efficacy of combining MEK-ERK inhibition with autophagy blockade.

Main Methods:

  • Utilized preclinical cancer models with KRAS mutations.
  • Administered MEK-ERK pathway inhibitors.
  • Assessed autophagic flux.
  • Combined MEK-ERK inhibition with autophagy blockade agents (chloroquine/hydroxychloroquine).

Main Results:

  • MEK-ERK inhibition induced autophagic flux in KRAS-mutated cancer models.
  • Autophagy blockade significantly enhanced the anti-cancer efficacy of MEK-ERK inhibitors.
  • Combination therapy showed improved outcomes in preclinical settings.

Conclusions:

  • Autophagic flux is a compensatory mechanism during MEK-ERK inhibition in KRAS-mutated cancers.
  • Combining MEK-ERK inhibitors with autophagy inhibitors (CQ/HCQ) represents a promising therapeutic strategy.
  • This combination warrants further clinical investigation for KRAS-driven cancers.
Keywords:
AMPKKRASMEK inhibitorautophagymetabolism

More Related Videos

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

1.1K
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

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

Published on: November 22, 2021

4.6K

Related Concept Videos

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...
8.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.7K
Dual Nature of Electromagnetic (EM) Radiation01:10

Dual Nature of Electromagnetic (EM) Radiation

Electromagnetic (EM) radiation consists of electric and magnetic field components oscillating in planes perpendicular to each other and mutually perpendicular to radiation propagation through space. EM radiation can be classified as a wave, characterized by the properties of waves such as wavelength (denoted as λ) and frequency (represented by ν).
Wavelength is the distance between two consecutive peaks (the highest point) or troughs (the lowest point) in the wave. Frequency is the number of...
3.7K
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
53.8K
What is Cancer?02:12

What is Cancer?

Cells and tissues must meticulously coordinate their activities for the normal functioning of the human body. Therefore, they exhibit socially responsible behavior - resting, growing, dividing, differentiating, or dying - for the organism’s benefit. Cancer arises when cells divide uncontrollably and invade other tissues or organs.
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
14.1K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
10.1K