scholarly journals EGFR-Targeted Therapy for Non-Small Cell Lung Cancer: Focus on EGFR Oncogenic Mutation

2013 ◽  
Vol 10 (3) ◽  
pp. 320-330 ◽  
Author(s):  
Alberto Antonicelli ◽  
Stefano Cafarotti ◽  
Alice Indini ◽  
Alessio Galli ◽  
Andrea Russo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Oncogenic Mutation

Acquired Resistance to Targeted Therapies in Advanced Non-Small Cell Lung Cancer: New Strategies and New Agents

2013 ◽  
pp. e272-e278
Author(s):  
Howard West ◽  
Geoffrey R. Oxnard ◽  
Robert C. Doebele
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Ongoing Research ◽  
Oncogenic Mutation

Although the transition to molecularly defined patient subgroups in advanced non-small cell lung cancer (NSCLC) often leads to dramatic and prolonged responses to an inhibitor of an identified oncogenic mutation, acquired resistance eventually ensues. The optimal approach to management in that setting remains the subject of ongoing research, although it is possible to identify several points that distinguish it from traditional tenets based on conventional chemotherapy. Such patients are not equivalent to those who have progressed on first-line chemotherapy, and consideration of initiation of chemotherapy-based regimens as if the patient were being treated first line in the absence of an oncogenic mutation is a reasonable consideration. Acquired resistance is often partial; therefore, continued treatment with the same targeted therapy or another agent against the same target is a strategy favored by many experts, in part to minimize the risk of “rebound progression” that may occur when the targeted therapy is withdrawn. Progression within the central nervous system (CNS) may occur because of poor penetration of the systemic targeted therapy into the CNS, rather than true cellular resistance to the therapy itself; accordingly, local therapy for “brain only” progression with sustained targeted therapy for extracranial disease can be associated with prolonged disease control. Finally, patients with acquired resistance to a targeted therapy are ideal candidates for clinical trials when available, particularly when repeat biopsies of progressing lesions can help elucidate mechanisms of resistance and thereby lead to histologically and molecularly informed treatment decisions.

scholarly journals Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Walter Z. Wang ◽  
Konstantin Shilo ◽  
Joseph M. Amann ◽  
Alyssa Shulman ◽  
Mohammad Hojjat-Farsangi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Small Cell ◽  
Orphan Receptor ◽  
Small Cell Lung ◽  
Sclc Patient

AbstractSmall cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

Bone Metastases and Non-Small Cell Lung Cancer: From Bisphosfonates to Targeted Therapy

2012 ◽  
Vol 19 (32) ◽  
pp. 5524-5535 ◽  
Author(s):  
A. Rossi ◽  
C. Gridelli ◽  
S. Ricciardi ◽  
F. de Marinis
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Bone Metastases ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Detecting resistance in EGFR-mutated non-small-cell lung cancer after clonal selection through targeted therapy

2015 ◽  
Vol 12 (2) ◽  
pp. 63-66 ◽  
Author(s):  
Justine L Kuiper ◽  
Idris Bahce ◽  
Charlotte Voorhoeve ◽  
Maqsood Yaqub ◽  
Daniëlle AM Heideman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clonal Selection ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated
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