Related Experiment Video

Updated: Jun 24, 2026

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

Targeting Ceramide Metabolism to Overcome Osimertinib Resistance in EGFR-mutant Non-Small Cell Lung Cancer: An In

Oğuzhan Selvi1, Canan Vejselova Sezer2, Mustafa Cengiz3

  • 1Medical Oncology Clinic, Bezmialem Vakif University Hospital, Istanbul, Türkiye.

Anti-Cancer Agents in Medicinal Chemistry
|June 23, 2026
PubMed
Abstract

Insights

New agents targeting ceramide metabolism, carmofur and B13, show promise against drug-resistant non-small cell lung cancer (NSCLC). These compounds effectively induced apoptosis in osimertinib-resistant NSCLC cells, suggesting a potential new therapeutic avenue for difficult-to-treat lung cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osimertinib is an epidermal growth factor receptor inhibitor used for non-small cell lung cancer (NSCLC) with T790M resistance mutations.
  • Acquired resistance to osimertinib limits its long-term efficacy in advanced NSCLC.
  • Investigating resistance mechanisms and alternative therapies is crucial for improving outcomes in NSCLC.

Purpose of the Study:

  • To evaluate the effectiveness of acid ceramidase inhibitors as alternative agents against NSCLC.
  • To assess the impact of carmofur and B13 on osimertinib-sensitive (H1975/OS) and osimertinib-resistant (H1975/OR) NSCLC cells.

Main Methods:

  • NSCLC cells were exposed to carmofur and B13 for 24, 48, and 72 hours.
  • Antiproliferative and cytotoxic effects were measured using the sulforhodamine B assay.
  • Proapoptotic activity was assessed via annexin V and caspase 3/7 assays; morphological changes were observed using confocal microscopy.

Main Results:

  • Carmofur and B13 demonstrated a proapoptotic effect in both osimertinib-sensitive and resistant NSCLC cell lines.
  • Carmofur exhibited moderate cytotoxicity, while B13 showed weak efficacy at tested concentrations.
  • Resistant NSCLC cells remained sensitive to carmofur and B13, suggesting ceramide metabolism is a viable therapeutic target.

Conclusions:

  • Carmofur and B13 are promising alternative therapeutic agents for drug-resistant NSCLC.
  • Targeting ceramide metabolism may overcome osimertinib resistance in NSCLC.
  • Further mechanistic and translational studies are warranted.
Keywords:
Osimertinibcarmofurconfocal microscopylung cancersulforhodamine B.

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

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

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 specific...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
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...