Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Antonio Russo, Francesco Passiglia, Ignacio Gil-Bazo, Marc Peeters, David S. Hong, Edgardo S. Santos, Francesco Passiglia, Patrick Pauwels, Christian Rolfo, Bivona, Luis E. Raez, Noemí Reguart, Elisa Giovannetti, Paul Germonpre, Mìquel Taron, Jan P. Van Meerbeeck, Lucio Buffoni, Rafael Rosell

Risultato della ricerca: Article

47 Citazioni (Scopus)

Abstract

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFRmutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arisefrom secondary EGFR mutations. Other resistance-inducing processes include mesenchymal–epithelialtransition factor (MET) amplification, epithelial–mesenchymal transformation, phenotypic change fromNSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeuticstrategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking ofmultiple members of the ErbB family. Several molecules which target multiple ErbB receptors are beinginvestigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitiniband lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance(T790M) mutations, are currently under clinical development. Other therapeutic strategies includeinhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodiesagainst the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptorregulation.Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises theimportance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeedcrucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimesin NSCLC.
Lingua originaleEnglish
pagine (da-a)990-1004
Numero di pagine15
RivistaCancer Treatment Reviews
Volume40
Stato di pubblicazionePublished - 2014

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Therapeutics
Adenosine Diphosphate Ribose
Somatomedin Receptors
HSP90 Heat-Shock Proteins
Mutation
Small Cell Lung Carcinoma
Sirolimus
Estrogens
Genotype
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cita questo

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. / Russo, Antonio; Passiglia, Francesco; Gil-Bazo, Ignacio; Peeters, Marc; Hong, David S.; Santos, Edgardo S.; Passiglia, Francesco; Pauwels, Patrick; Rolfo, Christian; Bivona; Raez, Luis E.; Reguart, Noemí; Giovannetti, Elisa; Germonpre, Paul; Taron, Mìquel; Van Meerbeeck, Jan P.; Buffoni, Lucio; Rosell, Rafael.

In: Cancer Treatment Reviews, Vol. 40, 2014, pag. 990-1004.

Risultato della ricerca: Article

Russo, A, Passiglia, F, Gil-Bazo, I, Peeters, M, Hong, DS, Santos, ES, Passiglia, F, Pauwels, P, Rolfo, C, Bivona, Raez, LE, Reguart, N, Giovannetti, E, Germonpre, P, Taron, M, Van Meerbeeck, JP, Buffoni, L & Rosell, R 2014, 'Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors', Cancer Treatment Reviews, vol. 40, pagg. 990-1004.
Russo, Antonio ; Passiglia, Francesco ; Gil-Bazo, Ignacio ; Peeters, Marc ; Hong, David S. ; Santos, Edgardo S. ; Passiglia, Francesco ; Pauwels, Patrick ; Rolfo, Christian ; Bivona ; Raez, Luis E. ; Reguart, Noemí ; Giovannetti, Elisa ; Germonpre, Paul ; Taron, Mìquel ; Van Meerbeeck, Jan P. ; Buffoni, Lucio ; Rosell, Rafael. / Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors. In: Cancer Treatment Reviews. 2014 ; Vol. 40. pagg. 990-1004.
@article{c3d2c4d62d794893ae4d139257f3f3f0,
title = "Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors",
abstract = "Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFRmutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arisefrom secondary EGFR mutations. Other resistance-inducing processes include mesenchymal–epithelialtransition factor (MET) amplification, epithelial–mesenchymal transformation, phenotypic change fromNSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeuticstrategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking ofmultiple members of the ErbB family. Several molecules which target multiple ErbB receptors are beinginvestigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitiniband lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance(T790M) mutations, are currently under clinical development. Other therapeutic strategies includeinhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodiesagainst the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptorregulation.Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises theimportance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeedcrucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimesin NSCLC.",
author = "Antonio Russo and Francesco Passiglia and Ignacio Gil-Bazo and Marc Peeters and Hong, {David S.} and Santos, {Edgardo S.} and Francesco Passiglia and Patrick Pauwels and Christian Rolfo and Bivona and Raez, {Luis E.} and Noem{\'i} Reguart and Elisa Giovannetti and Paul Germonpre and M{\`i}quel Taron and {Van Meerbeeck}, {Jan P.} and Lucio Buffoni and Rafael Rosell",
year = "2014",
language = "English",
volume = "40",
pages = "990--1004",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

AU - Russo, Antonio

AU - Passiglia, Francesco

AU - Gil-Bazo, Ignacio

AU - Peeters, Marc

AU - Hong, David S.

AU - Santos, Edgardo S.

AU - Passiglia, Francesco

AU - Pauwels, Patrick

AU - Rolfo, Christian

AU - Bivona, null

AU - Raez, Luis E.

AU - Reguart, Noemí

AU - Giovannetti, Elisa

AU - Germonpre, Paul

AU - Taron, Mìquel

AU - Van Meerbeeck, Jan P.

AU - Buffoni, Lucio

AU - Rosell, Rafael

PY - 2014

Y1 - 2014

N2 - Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFRmutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arisefrom secondary EGFR mutations. Other resistance-inducing processes include mesenchymal–epithelialtransition factor (MET) amplification, epithelial–mesenchymal transformation, phenotypic change fromNSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeuticstrategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking ofmultiple members of the ErbB family. Several molecules which target multiple ErbB receptors are beinginvestigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitiniband lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance(T790M) mutations, are currently under clinical development. Other therapeutic strategies includeinhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodiesagainst the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptorregulation.Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises theimportance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeedcrucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimesin NSCLC.

AB - Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFRmutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs.Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arisefrom secondary EGFR mutations. Other resistance-inducing processes include mesenchymal–epithelialtransition factor (MET) amplification, epithelial–mesenchymal transformation, phenotypic change fromNSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeuticstrategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking ofmultiple members of the ErbB family. Several molecules which target multiple ErbB receptors are beinginvestigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitiniband lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance(T790M) mutations, are currently under clinical development. Other therapeutic strategies includeinhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 orpoly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodiesagainst the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptorregulation.Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises theimportance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeedcrucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimesin NSCLC.

UR - http://hdl.handle.net/10447/99251

M3 - Article

VL - 40

SP - 990

EP - 1004

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

SN - 0305-7372

ER -