The place of targeted therapies in the management of non-small cell bronchial carcinoma. Molecular markers as predictors of tumor response and survival in lung cancer.
This review highlights the numerous molecular biology findings in the field of lung cancer with potential therapeutic impact in both the near and distant future. Abundant pre-clinical and clinical data indicate that BRCA1 mRNA expression is a differential modulator of chemotherapy sensitivity. Low levels predict cisplatin sensitivity and antimicrotubule drug resistance, and the opposite occurs with high levels. The main core of recent research has centered on epidermal growth factor receptor (EGFR) mutations and gene copy numbers. For the first time, EGFR mutations have been shown to predict dramatic responses in metastatic lung adenocarcinomas, with a threefold increase in time to progression and survival in patients receiving EGFR tyrosine-kinase inhibitors. Evidence has also been accumulated on the crosstalk between estrogen and EGFR receptor pathways, paving the way for clinical trials of EGFR tyrosine-kinase inhibitors plus aromatase inhibitors. Understanding the relevance of these findings can help to change the clinical practice in oncology towards customizing chemotherapy and targeted therapies, leading to improvement both in survival and in cost-effectiveness.
Rosell
R
R
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain. rrosell@ico.scs.es
Moran
T
T
Fernanda Salazar
M
M
Mendez
P
P
De Aguirre
I
I
Ramirez
J-L
JL
Isla
D
D
Cobo
M
M
Camps
C
C
Lopez-Vivanco
G
G
Alberola
V
V
Taron
M
M
D015415:Biomarkers; D002283:Carcinoma, Bronchogenic / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D009154:Mutation; D011379:Prognosis; D015996:Survival Rate
D015415:Biomarkers