Related Experiment Video

Updated: Apr 16, 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

RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer

Matthew J Niederst1, Lecia V Sequist1, John T Poirier2

  • 11] Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.

Nature Communications
|March 12, 2015
PubMed

Insights

Resistance to lung cancer drugs often involves a switch from non-small-cell lung cancer (NSCLC) to small-cell lung cancer (SCLC). This transformation involves loss of Retinoblastoma (RB) protein and adoption of SCLC characteristics.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tyrosine kinase inhibitors (TKIs) are effective for EGFR-mutated non-small-cell lung cancer (NSCLC).
  • Relapse is common within a year, with some cases transforming into small-cell lung cancer (SCLC).
  • The molecular drivers of this NSCLC to SCLC transformation are largely unknown.

Purpose of the Study:

  • To investigate the molecular changes associated with histological transformation in resistant EGFR-mutated NSCLC.
  • To identify key molecular events driving the transition to SCLC.

Main Methods:

  • Analysis of tumor samples and cell lines from patients with resistant EGFR-mutated NSCLC.
  • Assessment of Retinoblastoma (RB) protein expression.
  • Evaluation of neuroendocrine markers and EGFR expression levels.
  • Testing sensitivity to BCL2 family inhibition.

Main Results:

  • Loss of Retinoblastoma (RB) protein was observed in 100% of SCLC-transformed resistant NSCLC cases.
  • RB loss was rare in resistant NSCLC cases that did not transform.
  • SCLC-transformed cancers showed increased neuroendocrine markers and decreased EGFR expression.
  • Resistant SCLC-transformed cancers exhibited greater sensitivity to BCL2 family inhibition compared to resistant NSCLCs.

Conclusions:

  • Loss of RB is a key event in the transformation of EGFR-mutated NSCLC to SCLC.
  • Resistant NSCLC acquires SCLC-like molecular and phenotypic characteristics during transformation.
  • These findings provide insights into therapeutic resistance mechanisms in lung cancer.

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.5K
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

25.2K

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