Related Experiment Video

Updated: Jan 17, 2026

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

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

Published on: June 26, 2019

8.4K

Assembly factor for spindle microtubules (ASPM) promotes osimertinib resistance in lung cancer by increasing EGFR

Pengpeng Gui1,2,3, Zhengyi Han1, Zhenyu Yin2

  • 1State Key Laboratory of Technologies for Chinese Medicine Pharmaceutica Process Control and intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.

Frontiers in Genetics
|September 22, 2025
PubMed
Abstract

Insights

Assembly factor for spindle microtubules (ASPM) drives non-small cell lung cancer (NSCLC) aggressiveness and EGFR tyrosine kinase inhibitor (EGFR-TKI) resistance. Targeting ASPM may overcome resistance and improve NSCLC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), is a major cause of cancer mortality.
  • Epidermal growth factor receptor (EGFR) mutations are key targets for NSCLC therapy, but resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) is a significant clinical hurdle.
  • Identifying novel molecular drivers of EGFR-TKI resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of the assembly factor for spindle microtubules (ASPM) in NSCLC progression and resistance to EGFR-TKIs.
  • To explore ASPM as a potential therapeutic target for overcoming drug resistance in NSCLC.

Main Methods:

  • Bioinformatic analysis of NSCLC tumor tissue datasets to assess ASPM expression and its correlation with patient survival.
  • Functional studies using EGFR-TKI-resistant NSCLC cell lines (PC9-OR) with ASPM-silenced models.
  • Evaluation of cellular proliferation, invasion, cell cycle, EGFR protein stability, and response to osimertinib treatment.

Main Results:

  • ASPM was found to be significantly upregulated in NSCLC tissues, correlating with reduced patient survival.
  • ASPM silencing suppressed malignant phenotypes (proliferation, invasion) in NSCLC cells and sensitized resistant cells to osimertinib.
  • Inhibition of ASPM reduced cell cycle damage and EGFR protein instability in resistant cells, restoring EGFR expression and function.

Conclusions:

  • ASPM acts as a novel regulator of EGFR-TKI resistance in NSCLC, promoting tumor aggressiveness and stabilizing EGFR signaling.
  • Targeting ASPM presents a promising strategy to overcome EGFR-TKI resistance and enhance the efficacy of osimertinib.
  • These findings support the development of ASPM-directed therapies for precision oncology in refractory NSCLC.
Keywords:
EGFR mutationEGFR-TKI resistanceassembly factor for spindle microtubules (ASPM)non-small cell lung cancer (NSCLC)osimertinibtumor invasiveness

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

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

9.2K
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

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...
7.7K
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...
3.7K
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...
4.6K
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...
8.6K