Title of article :
Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors
Author/Authors :
Rolfo، نويسنده , , Christian and Giovannetti، نويسنده , , Elisa and Hong، نويسنده , , David S. and Bivona، نويسنده , , T. and Raez، نويسنده , , Luis E. and Bronte، نويسنده , , Giuseppe and Buffoni، نويسنده , , Lucio and Reguart، نويسنده , , Noemي and Santos، نويسنده , , Edgardo S. and Germonpre، نويسنده , , Paul and Taron، نويسنده , , Mىquel and Passiglia، نويسنده , , Francesco and Van Meerbeeck، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2014
Abstract :
AbstractIntroduction
ent with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.
covered
eview examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal–epithelial transition factor (MET) amplification, epithelial–mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or poly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation.
sion
ed understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC.
Keywords :
EGFR mutations , TKI inhibitors resistance , NSCLC , New drugs , Novel therapeutic strategies
Journal title :
Cancer Treatment Reviews
Journal title :
Cancer Treatment Reviews