Related Experiment Video

Updated: Jun 30, 2025

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.0K

From osimertinib to preemptive combinations

Mikhail V Blagosklonny1

  • 1Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Oncotarget
|March 18, 2024
PubMed

Insights

First-line osimertinib improves median progression-free survival (PFS) for EGFR-mutant lung cancer but can harm some patients. Preemptive combination therapy offers a potential solution to increase PFS for most patients without harm.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Epidermal growth factor receptor (EGFR) mutations drive lung cancer.
  • Osimertinib is a first-line treatment for EGFR-mutant lung cancer, extending median progression-free survival (PFS).
  • However, a subset of patients experiences reduced PFS with osimertinib compared to earlier treatments.

Purpose of the Study:

  • To evaluate the potential harm of first-line osimertinib in a subset of EGFR-mutant lung cancer patients.
  • To propose preemptive combination (PC) therapies to improve PFS and avoid harm.
  • To explore PCs for MET-driven lung cancer.

Main Methods:

  • Comparative analysis of PFS data for osimertinib versus first-generation TKIs.
  • Conceptualization of preemptive combination therapies.
  • Exploration of treatment strategies for MET-driven lung cancer.

Main Results:

  • First-line osimertinib extends median PFS but reduces individual PFS in 15-20% of patients.
  • A comprehensive PC of osimertinib, afatinib/gefitinib, and capmatinib could significantly increase PFS for 80% of patients.
  • The proposed PCs aim to maximize PFS benefits without causing harm.

Conclusions:

  • Osimertinib is essential for first-line treatment due to overall median PFS gains, despite potential individual harm.
  • Preemptive combination therapy represents a promising strategy to enhance treatment efficacy and patient outcomes in EGFR-mutant and MET-driven lung cancer.
  • Further research into comprehensive preemptive combinations is warranted.
Keywords:
EGFRNSCLCafatinibcapmatinibgefitiniblung cancerresistance

More Related Videos

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

2.8K
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

8.0K

Related Concept Videos

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...
4.9K
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...
7.6K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
524
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
164
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...
6.5K