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Updated: Aug 16, 2026
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
[News about targeted therapies in non-small-cell lung cancer in 2015 (except immuno-therapy)]
Cécile Hamard1, Anne-Marie Ruppert2, Armelle Lavole3
1GRC 04 UPMC, hôpital Tenon, Assistance Publique-hôpitaux de Paris, 4, rue de la Chine, 75970 Paris cedex 20, France.
Abstract:
Recently, developments of therapies that target abnormally activated signaling pathways are increasing for patients with non-small cell lung cancer. EGFR mutations are found in about 10% of lung cancers, especially in adenocarcinoma, women and non-smokers. Three EGFR inhibitors (erlotinib, gefitinib and afatinib) received a European marketing authorization for up to first line treatment of EGFR mutated NSCLC. Effectiveness of EGFR inhibitors is higher than conventional chemotherapy. Third generation EGFR inhibitors (rociletinib, AZD9291) are effective for patients who develop a resistance mutation such as T790M resistance mutation; they obtained temporary authorization for use in France in 2015. The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line. Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib. INCA supports ACSé program evaluating the efficacy of crizotinib in NSCLC amplified for MET or translocated for ROS1 and ACSé program evaluating the efficacy of vemurafenib in tumors non melanoma mutated V600E BRAF. The role of other biomarkers such as KRAS, BRAF, HER2 and PI3KCA mutations remains to be defined in NSCLC.
Insights
Targeted therapies for non-small cell lung cancer (NSCLC) show promise. Epidermal growth factor receptor (EGFR) inhibitors and anaplastic lymphoma kinase (ALK) inhibitors are effective for specific NSCLC mutations.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) treatment is evolving with targeted therapies.
- Specific genetic mutations, like EGFR and EML4-ALK, drive NSCLC growth in certain patient populations.
- Conventional chemotherapy has limitations, prompting the development of molecularly targeted drugs.
Purpose of the Study:
- To review the current landscape of targeted therapies for NSCLC.
- To highlight the efficacy of EGFR and ALK inhibitors in specific NSCLC subtypes.
- To discuss emerging therapies and the role of other biomarkers.
Main Methods:
- Review of recent clinical trial data and European marketing authorizations.
- Analysis of targeted therapies based on specific genetic alterations (EGFR mutations, ALK translocations).
- Discussion of resistance mechanisms and third-generation inhibitors.
Main Results:
- EGFR inhibitors (erlotinib, gefitinib, afatinib) are effective first-line treatments for EGFR-mutated NSCLC.
- Third-generation EGFR inhibitors show efficacy against T790M resistance mutations.
- Crizotinib and ceritinib are established treatments for ALK-translocated NSCLC, with ongoing research for other targets like MET, ROS1, and BRAF.
Conclusions:
- Targeted therapies have significantly improved outcomes for NSCLC patients with specific driver mutations.
- Further research is needed to define the role of other biomarkers (KRAS, BRAF, HER2, PI3KCA) in NSCLC treatment.
- Personalized medicine approaches based on molecular profiling are crucial for optimizing NSCLC therapy.
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