Related Experiment Video

Updated: Apr 14, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.3K

Multiple myeloma acquires resistance to EGFR inhibitor via induction of pentose phosphate pathway

Yan Chen1, Ruibin Huang1, Jianghua Ding1

  • 1Department of Haematology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.

Scientific Reports
|April 21, 2015
PubMed

Insights

EGFR inhibitors show moderate efficacy in triple-wildtype multiple myeloma (MM) by inducing the pentose phosphate pathway (PPP). Combining EGFR inhibition with PPP inhibitors offers synergistic effects in MM treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma (MM) often exhibits mutations in KRAS/NRAS/BRAF within the epidermal growth factor receptor (EGFR) pathway, leading to resistance against EGFR inhibitors.
  • Understanding the molecular mechanisms underlying MM response to targeted therapies is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To investigate the efficacy of EGFR inhibition in multiple myeloma cells with different mutational statuses.
  • To elucidate the role of the pentose phosphate pathway (PPP) in mediating resistance or sensitivity to EGFR inhibitors in MM.
  • To explore combination therapies involving EGFR and PPP inhibitors for MM treatment.

Main Methods:

  • Cell culture of multiple myeloma cell lines with varying KRAS/NRAS/BRAF/EGFR pathway mutations.
  • Treatment with EGFR inhibitors (Gefitinib, Afatinib) and PPP inhibitor (6AN).
  • Assessment of cell viability, pathway activation (PPP, NADPH levels), and synergistic effects.
  • Genetic silencing of EGFR, ERBB2, and mTOR pathways.

Main Results:

  • EGFR inhibition showed moderate efficacy only in KRAS/NRAS/BRAF wildtype (triple-WT) MM cells; no effect was observed in cells with mutations.
  • Gefitinib treatment induced the pentose phosphate pathway (PPP) in triple-WT MM cells, contributing to the moderate inhibitory effect.
  • Combination of Gefitinib with 6AN (PPP inhibitor) resulted in synergistic inhibition in triple-WT cells, which could be reversed by NADPH addition.
  • Dual EGFR/ERBB2 inhibition with Afatinib yielded similar outcomes, and genetic silencing suggested ERBB2's major effect converged through the EGFR pathway.

Conclusions:

  • EGFR pathway mutations significantly impact the response of multiple myeloma cells to EGFR inhibitors.
  • The pentose phosphate pathway (PPP) plays a critical role in the resistance mechanism of MM cells to EGFR inhibitors.
  • Combination therapy targeting both EGFR and PPP pathways, or ERBB2, holds promise for a subset of MM patients, paving the way for individualized targeted therapies.

More Related Videos

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.7K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

931

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...
8.5K
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
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
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K
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...
5.4K