scholarly journals Loss of EGFR Mutation Expression Induced by NF1 Mutation in Non-Small Cell Lung Cancer: Non-Canonical Pathway of Tyrosine Kinase Inhibitors’ Resistance

2021 ◽  
Vol 18 (01) ◽  
Author(s):  
Jose Gabriel Negron Rodriguez ◽  
Luis Orrego Poma ◽  
Manuel Leiva Galvez ◽  
Maria Claudia Rodriguez Zavaleta ◽  
Wuilbert Rodriguez Pantigoso
Keyword(s):  
Cellular Proliferation ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Canonical Pathway ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Apoptosis Resistance ◽  
Cell Lung Carcinoma ◽  
Egfr Expression

Non-small cell lung carcinoma (NSCLC) is considered the first cause of cancer-related death worldwide and many therapies have been developed against the presence of actionable mutations. For example, targeting the EGFR mutation has changed the overall prognosis in NSCLC. However, resistance to treatment has emerged and many canonical mechanisms have already been described. NF1 mutation causes partial or total loss of function of neurofibromin, which activates several intracellular pathways (MAPK / ERK, PI3K / AKT, TGF -β / Smad), producing cellular proliferation, migration, apoptosis resistance and genetic instability, leading to loss of EGFR expression. Herein, we describe a case of a novel activation of a non-canonical pathway that led to treatment resistance by NF1 mutation.

scholarly journals Correction: PKCα is required for Akt-mTORC1 activation in non-small cell lung carcinoma (NSCLC) with EGFR mutation

Oncogene ◽  
2019 ◽  
Vol 38 (48) ◽  
pp. 7366-7366
Author(s):  
Mohamed F. Salama ◽  
Mengling Liu ◽  
Christopher J. Clarke ◽  
Mel Pilar Espaillat ◽  
John D. Haley ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Mtorc1 Activation

Real-world evidence in the treatment of metastatic non-small cell lung cancer in a single institution of Colombia in the period August 2015 to August 2018.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18204-e18204
Author(s):  
Luis Eduardo Pino ◽  
Aylen Vanessa Ospina Serrano ◽  
Ivan Camilo Triana
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Target Therapy ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Cell Lung Carcinoma

e18204 Background: In Colombia, lung cancer is the first cause of mortality. However, there is a large gap in terms of the information available regarding the characteristics and survival of these patients in the country. Methods: This is an observational, descriptive study of a cohort of patients with stage IV non-small cell lung carcinoma who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, oncogenic addiction expression, PDL1 expression, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. Results: Twenty-six patients were included during the 3 years. The OSm for all the cohort was 19.6 months(m). In the group without PDL-1 expression and negative for oncogenic addiction that received treatment with chemotherapy the OSm was 16.9m and the PFS 9.6m. The OSm for the group with EGFR mutation that received target therapy was 24,7m and the PFS 13.11m. The patients with ALK rearrangement treated with target therapy had an OSm 17m and PFS 5m. The group with expression greater than 50% for PDL-1 that received only immunotherapy OSm was 9.5m and PFS 9m, and in the group with expression for PDL-1 between 1-49% the median OSm and PFS has not been reached. In relation with grade 3 toxicity, 7% of patients that received chemotherapy had kidney failure, 7% emesis and 15% hyporexia. Patients that received target therapy 9% had diarrhea and 9% hepatotoxicity. 9% of patients with bevacizumab presented bleeding and 8% of patients with immunotherapy had autoimmune colitis, in all these cases the medication was suspended. Hypothyroidism was the most frequent complication with the immunotherapy, and it was resolved with substitution therapy. Conclusions: Clinical characteristics and outcomes of this cohort were similar to other lung cancer patients series. Factors like cigarette, nutritional status and ECOG were no significant in the survival. 34,6% of patients had EGFR mutation and 7% had ALK rearrangements. Related to PDL1 we found 26% expresser patients. The highest OS and PFS was for the group with the EGFR mutation and for the group with PDL-1 expression between 1-49%.

Erlotinib monotherapy in the treatment of advanced non-small cell lung carcinoma: A single center experience with 187 patients from 2005-2018.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20718-e20718
Author(s):  
Felipe Matsunaga ◽  
David Pfau ◽  
Kai Laukamp ◽  
Elias Kikano ◽  
Nikhil H. Ramaiya ◽  
...  
Keyword(s):  
Adverse Events ◽  
Tyrosine Kinase ◽  
Lung Carcinoma ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Egfr Mutant ◽  
Lung Biopsies

e20718 Background: Inhibition of epidermal growth factor receptors (EGFR) bearing somatic mutations in the tyrosine kinase domain is an important molecular target in the treatment of advanced non-small cell lung carcinoma (NSCLC). As such, first generation tyrosine kinase inhibitors such as erlotinib have been adopted as standard of care in the treatment of EGFR mutation positive advanced NSCLC. Herein we describe our experience with erlotinib monotherapy since its approval for clinical use in the United States in late 2004. Methods: A retrospective analysis of 187 patients with a diagnosis of NSCLC who underwent erlotinib monotherapy from 2005-2018 was performed. Clinical variables including patient age, disease stage, EGFR genomic status, adverse events and survival were analyzed. Likelihood Ratio Chi-Square test was applied and statistical significance was set to p < 0.05. Results: Among all patients who received erlotinib monotherapy (n = 187), treatment duration longer than 3 months was associated with EGFR mutant status (p < 0.001), increased rates of repeat lung biopsies (p < 0.002) as well as pulmonary (p = 0.008), gastrointestinal (p = 0.005) and cutaneous adverse events (p = 0.005). Subgroup analysis based on EGFR genomic status (n = 71) revealed that EGFR mutation positive patients remained on erlotinib for at least three months at a higher rate than wildtypes (p < 0.001), but also sustained higher rates of lung re-biopsy (p = 0.0121) and concomitant gastrointestinal (diarrhea) and cutaneous (acneiform, maculopapular rashes) adverse events (grades 1-3) (p = 0.003). EGFR mutant status was associated with increased rates of survival of 12 months or greater since the initiation of erlotinib (p < 0.001). Conclusions: Erlotinib monotherapy duration greater than 3 months and EGFR mutant status are associated with significantly higher rates of repeat lung biopsies and gastrointestinal and cutaneous adverse events. EGFR mutant status is further associated with survival of greater than 1 year.

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