Comparative study on the efficacy and exposure of molecular target agents in non-small cell lung cancer PDX models with driver genetic alterations

2021 ◽  
pp. molcanther.0371.2021
Author(s):  
Hitomi Jo ◽  
Shigehiro Yagishita ◽  
Yoshiharu Hayashi ◽  
Shoraku Ryu ◽  
Mikiko Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Comparative Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Molecular Target ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pdx Models

Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists

2020 ◽  
Vol 16 (1) ◽  
pp. 5-10
Author(s):  
Adrien Costantini ◽  
Theodoros Katsikas ◽  
Clementine Bostantzoglou
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Standard Of Care ◽  
Genetic Alterations ◽  
Small Cell ◽  
Extensive Literature ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma ◽  
Mutational Status

Over the past decade, major breakthroughs in the understanding of lung cancer histology and mutational pathways have radically changed diagnosis and management. More specifically, in non-small cell lung cancer (NSCLC), tumour characterisation has shifted from differentiating based solely on histology to characterisation that includes genetic profiling and mutational status of Epidermal Growth Factor (EGFR), Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF. These genetic alterations can be targeted by specific drugs that result in improved progression-free survival, as well as higher response rates and are currently standard of care for NSCLC patients harbouring these mutations. In this a narrative, non-systematic review we aim to handpick through the extensive literature and critically present the ground-breaking studies that lead to the institution of tailored treatment options as the standard of care for the main targetable genetic alterations.

Improvements in access to cancer clinical trials facilitated by comprehensive genomic profiling in non-small cell lung cancer.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 59-59
Author(s):  
Woojung Lee ◽  
Scott Spencer ◽  
Josh John Carlson ◽  
Tam Dinh ◽  
Victoria Dayer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung ◽  
Eligibility Criteria ◽  
Comprehensive Genomic Profiling

59 Background: The use of comprehensive genomic profiling (CGP) in cancer patients could lead to additional enrollment in clinical trials that study novel genetic biomarkers, potentially reducing treatment costs for payers and improving health outcomes for patients. Our objective was to estimate the number of additional clinical trials in which patients with non-small cell lung cancer (NSCLC) could potentially enroll due to the use of CGP vs. a comparator panel of 50 genes or less. Methods: Clinical trials in NSCLC that started between 2015 - 2020 were identified from the Aggregate Analysis of ClinicalTrials.gov (AACT) database. Trials with unknown status or study sites outside the United States only were excluded. We abstracted information on required genetic alterations based on the study eligibility criteria. We calculated the incremental number of trials available to patients due to results generated by CGP (FoundationOne CDx, 324 genes) vs. a commercially available comparator panel that was 50 genes or less (Oncomine Dx Target Test, 23 genes) by phase and calendar year. The additional trials were characterized by disease severity, type of therapy, and setting. Results: Enrollment eligibility was dependent on genetic variant status in 35% (250/709) of all identified NSCLC trials. There were 29 (248 vs. 219) additional clinical trials available to patients through the use of CGP, 12% of all gene-specific trials for NSCLC. We identified 45 uses of genetic markers in the 29 additional clinical trials. The most frequent genetic marker in the incremental trials was microsatellite instability, accounting for 44% of all identified markers (20/45). The incremental number of trials available to patients due to the use of CGP did not vary significantly over time but varied by phase – most of the additional clinical trials were in phase 1 or 2 (28/29, 97%). Most of the incremental trials were in metastatic disease (22/29, 76%) and were conducted in academic or advanced community settings (18/29, 62%). The most frequently studied type of intervention in these studies was targeted monotherapy (8/29, 28%), followed by immuno-monotherapy (7/29, 24%). Conclusions: Clinical trials in NSCLC initiated over the past 5 years have consistently included CGP-specific genes or markers in eligibility criteria. Patients with NSCLC have the potential to benefit from the use of CGP as compared to smaller gene panels through improved access to clinical trials.[Table: see text]

scholarly journals Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 245 ◽  
Author(s):  
Yosuke Miura ◽  
Noriaki Sunaga
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Direction ◽  
Nsclc Patients

The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

scholarly journals PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations

2016 ◽  
Vol 5 (5) ◽  
pp. e1131379 ◽  
Author(s):  
Andreas H. Scheel ◽  
Sascha Ansén ◽  
Anne M. Schultheis ◽  
Matthias Scheffler ◽  
Rieke N. Fischer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 690 ◽  
Author(s):  
Arik Bernard Schulze ◽  
Georg Evers ◽  
Andrea Kerkhoff ◽  
Michael Mohr ◽  
Christoph Schliemann ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Molecular Pathways ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Therapeutic Concept ◽  
Platinum Based Chemotherapy

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called ‘poly-(ADP)-ribose polymerases’ (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of ‘enhancer of zeste homolog 2’ (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.

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