Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer

JF Gainor, L Dardaei, S Yoda, L Friboulet, I Leshchiner… - Cancer discovery, 2016 - AACR
Advanced, anaplastic lymphoma kinase (ALK)–positive lung cancer is currently treated with
the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK …

Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers

R Katayama, AT Shaw, TM Khan… - Science translational …, 2012 - science.org
Most anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancers (NSCLCs)
are highly responsive to treatment with ALK tyrosine kinase inhibitors (TKIs). However …

I1171 missense mutation (particularly I1171N) is a common resistance mutation in ALK-positive NSCLC patients who have progressive disease while on alectinib and …

SHI Ou, J Greenbowe, ZU Khan, MC Azada, JS Ross… - Lung cancer, 2015 - Elsevier
Objectives Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors
such as crizotinib and alectinib have been documented in non-small cell lung cancer …

ALK mutations conferring differential resistance to structurally diverse ALK inhibitors

JM Heuckmann, M Hölzel, ML Sos, S Heynck… - Clinical Cancer …, 2011 - AACR
Purpose: EML4–ALK fusions define a subset of lung cancers that can be effectively treated
with anaplastic lymphoma kinase (ALK) inhibitors. Unfortunately, the duration of response is …

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

PL Chia, P Mitchell, A Dobrovic, T John - Clinical epidemiology, 2014 - Taylor & Francis
Improved understanding of molecular drivers of carcinogenesis has led to significant
progress in the management of lung cancer. Patients with non-small-cell lung cancer …

Updated evidence on the mechanisms of resistance to ALK inhibitors and strategies to overcome such resistance: clinical and preclinical data

G Toyokawa, T Seto - Oncology research and treatment, 2015 - karger.com
Anaplastic lymphoma kinase (ALK) rearrangement is one of the oncogenes in non-small cell
lung cancer (NSCLC) identified in 2007. The PROFILE trials demonstrated that patients with …

[HTML][HTML] Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer

S Kim, TM Kim, DW Kim, H Go, B Keam, SH Lee… - Journal of Thoracic …, 2013 - Elsevier
Background Anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer
(NSCLC) is markedly sensitive to the ALK inhibitor crizotinib. However, acquired resistance …

ALK in Lung Cancer: Past, Present, and Future

AT Shaw, JA Engelman - Journal of clinical oncology, 2013 - ascopubs.org
In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements
are present in a small subset of non–small-cell lung cancers. ALK-positive cancers are …

Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK Mutations in ALK-Positive Lung Cancer

S Yoda, JJ Lin, MS Lawrence, BJ Burke, L Friboulet… - Cancer discovery, 2018 - AACR
The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy
with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor …

[HTML][HTML] Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib …

SHI Ou, M Azada, DJ Hsiang, JM Herman… - Journal of Thoracic …, 2014 - Elsevier
Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been
identified in ALK-rearranged (ALK+) non–small-cell lung cancer (NSCLC) patients who …