Related Experiment Video

Updated: Jan 14, 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

KRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors

Iris Z Uras1, Marija V Trkulja2, Abdelrahman K A A Salama2

  • 1Institute of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria. iris.uras@meduniwien.ac.at.

NPJ Precision Oncology
|January 12, 2026
PubMed

Insights

Combining ERBB and Aurora kinase (AURK) inhibition overcomes resistance in KRAS-mutant lung adenocarcinoma (LUAD). This dual-targeting strategy enhances current therapies, offering improved durability and combating acquired resistance in LUAD patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • KRAS mutations are common drivers in lung adenocarcinoma (LUAD).
  • KRAS-targeted therapies show limited durability due to rapid resistance development.
  • Novel therapeutic strategies are crucial for improving outcomes in KRAS-mutant LUAD.

Purpose of the Study:

  • To identify novel therapeutic strategies to overcome resistance in KRAS-mutant LUAD.
  • To investigate the synergistic effects of ERBB and Aurora kinase (AURK) inhibition in LUAD models.
  • To elucidate the mechanisms underlying ERBB/AURK co-inhibition efficacy.

Main Methods:

  • High-throughput drug screening to identify sensitizing agents.
  • In vitro assays assessing cell viability, clonogenicity, and apoptosis.
  • In vivo studies evaluating tumor growth inhibition.
  • Phospho-proteomic and transcriptomic analyses to determine molecular mechanisms.

Main Results:

  • Aurora kinase (AURK) inhibitors potentiated afatinib efficacy in KRAS-mutant LUAD models.
  • ERBB/AURK co-inhibition synergistically suppressed tumor growth, induced apoptosis, and caused G2→M cell cycle arrest.
  • Dual inhibition disrupted compensatory signaling pathways, including EGFR and ERK.
  • Co-targeting ERBB and AURK overcame resistance in afatinib- and sotorasib-refractory models.

Conclusions:

  • ERBB/AURK co-inhibition is a promising strategy to enhance the efficacy of KRAS-targeted therapies in LUAD.
  • This approach effectively combats acquired resistance by targeting bypass signaling pathways.
  • Dual inhibition offers a potential therapeutic avenue to improve response durability in KRAS-driven LUAD.

More Related Videos

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

24.9K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

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

18.5K

Related Concept Videos

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
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...
5.3K
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...
5.1K