Related Experiment Video

Updated: Oct 11, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.1K

Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids

Ke Gong1,2, Gao Guo1, Nicole A Beckley1

  • 1Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Nature Communications
|December 2, 2021
PubMed

Insights

Prednisone effectively suppresses adaptive resistance to EGFR inhibitors in NSCLC by blocking multiple inflammatory pathways. This broad suppression is superior to single-target TNF inhibitors, offering a promising strategy for durable tumor growth inhibition.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Receptor tyrosine kinase (RTK) pathway inhibition in cancer can induce adaptive resistance.
  • Tumor necrosis factor (TNF) upregulation is a key adaptive response to epidermal growth factor receptor (EGFR) inhibition in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To compare the efficacy of prednisone, thalidomide, and etanercept in blunting adaptive resistance to EGFR inhibitors.
  • To investigate the mechanisms by which prednisone suppresses adaptive resistance signals.

Main Methods:

  • Comparison of TNF inhibitors (etanercept, thalidomide, prednisone) in preclinical NSCLC models.
  • Assessment of inflammatory signals, bypass RTK signaling, and resistance pathways (STAT3, YAP, TNF-NF-κB).
  • Evaluation of combination therapy efficacy in suppressing tumor growth in mouse models.

Main Results:

  • Prednisone demonstrated superior suppression of EGFR inhibition-induced inflammatory signals compared to etanercept and thalidomide.
  • Prednisone effectively shut down bypass RTK signaling and inhibited key resistance mediators like STAT3, YAP, and TNF-NF-κB.
  • Combination therapy with prednisone and EGFR inhibition significantly outperformed etanercept or thalidomide in durable tumor growth suppression.

Conclusions:

  • Broad suppression of adaptive resistance signals is more effective than targeting a single component.
  • Prednisone is identified as a potent inhibitor of adaptive resistance with acceptable toxicity in NSCLC and potentially other cancers.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.4K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.2K

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...
7.9K
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
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...
4.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
237