7IN - The characterization of lung cancer

Date 01 October 2012
Event ESMO Congress 2012
Session The characterization of lung cancer in multiple different diseases
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Jean-Charles Soria
Authors J. Soria
  • Medicine Department, Institut Gustave Roussy, 94805 - Villejuif/FR

Abstract

The characterization of lung cancer Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer is currently being revisited on the basis of modern molecular portraits that allow the identification of new molecular subtypes. Larges scale studies have identified frequent mutations mainly in TP53, RB1, CDKN2A, and STK11 tumor suppressor and in EGFR, KRAS and NRAS oncogenes. Many other molecular abnormalities have been reported in other genes such as PI3K, PTEN, AKT1, MDM2, APC, HER2, KDR, MET, CTNNB1, ATM, BRAF, AKT1 and more recently ALK, RET, ROS as well as FGFR1. Beyond the now classical oncogene-drivers represented by EGFR mutation and ALK translocation, many other molecular abnormalities could be used for selection of specific therapy such as amplification of HER2 and FGFR1, translocation of RET or ROS, or activating mutations of HER2, HER3, HER4, FGFR2 … Nevertheless the correlation between the presence of such abnormalities and clinical response are not definitively documented, although some interesting small series or case reports have been reported. The table below provides a summary of specific alterations, their frequencies and their potential corresponding molecular targeted interventions. DNA repair players are also potential predictors of standard anti-cancer therapies (ERCC1, MSH2, BRCA1, PARP). In summary, characterization of the genomic changes that drive an individual patient's disease is now critical to inform rationally targeted therapies and treatment planning for patients with NSCLC. Table: 71N

Molecular alteration Frequency in Adenocarcinoma Frequency in Squamous cell carcinoma Potential Drugs
EGFR mutation 10-40% 2-5% Gefitinib Erlotinib Afatinib PF-00299804
EML4-ALK translocation 5-7% Rare Crizotinib, ASP3026, AP26113, CH5424802 LDK-378 HSP90 inhibitors
ROS translocation 2% Rare Crizotinib, ASP3026, AP26113, CH5424802 LDK-378 HSP90 inhibitors
RET translocation 6% Rare Vandetanib
HER2 mutation or amplification 2% 6% Rare 2% Trastuzumab PF-00299804 Afatinib
PI3K mutation or amplification 5% < 10% 5% < 10% GDC-0941 GDC 0980XL-147XL-765BEZ-235BKM120 BYL 719 PF-05212384
MET amplification < 10% < 10% XL184 ARQ917 MetMab
RAS mutation RAF mutation 10-30% 3% 5% 2% Sorafenib AZD6244; GSK1120212; AS703026, RO4987655 MEK162
FGFR1 amplification 5% 20% BJG398, AZD4547, TKI258 EOS 3810

Disclosure

The author has declared no conflicts of interest.