scholarly journals Progress in target therapy of advanced non-small cell lung cancer

2021 ◽  
Vol 3 (4) ◽  
pp. 17
Author(s):  
Li Zhang ◽  
Rui Cao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Durvalumab in the treatment of locally advanced non-small cell lung cancer after chemoradiotherapy in a real practice

2019 ◽  
Vol 21 (3) ◽  
pp. 21-25
Author(s):  
Dina D Sakaeva ◽  
Valerii V Ruchkin ◽  
Olga V Goncharova ◽  
Raliia R Abbasova ◽  
Fagim F Mufazalov
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Locally Advanced ◽  
Complete Response ◽  
Small Cell ◽  
Clinical Practices ◽  
Small Cell Lung ◽  
The Pacific

In 2017 the first published PFS results of PACIFIC study demonstrated new opportunities of immunotherapy in locally-advanced unresectable non-small-cell lung cancer (NSCLC) after chemoradiation (CRT). The positive overall survival results in this trial were received next year. This trial has become the first positive study in the more then 10 years after failure of all trials which investigated different approaches for improvement efficacy of standard CRT (induction therapy, consolidation therapy, target therapy, increased RT dose). The PACIFIC trial has opened new opportunities to improve outcomes in this patient’s population. Durvalumab was registered in Russia in July 2019, however clinical experience of durvalumab administration is still limited and we need to build expertise in this field. In this article we present the first example of durvalumab therapy in post CRT period in Bashkortostan real clinical practices. Patient with IIIB st NSCLC started durvalumab therapy after standard CRT. The complete response was registered after 4 months of therapy and currently after 9 months of therapy it is still remain.

scholarly journals Resistance to KRASG12C Inhibitors in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Juan Bautista Blaquier ◽  
Andrés Felipe Cardona ◽  
Gonzalo Recondo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Target Therapy ◽  
Phase 1 ◽  
Small Cell ◽  
Small Cell Lung ◽  
Intrinsic Resistance ◽  
Secondary Resistance

KRAS mutations are one of the most prevalent oncogenic alterations in cancer. Until recently, drug development targeting KRAS did not convey clinical benefits to patients. Specific KRASG12C inhibitors, such as sotorasib and adagrasib, have been designed to bind to the protein’s mutant structure and block KRASG12C in its GDP-bound inactive state. Phase 1/2 trials have shown promising anti-tumor activity, especially in pretreated non-small cell lung cancer patients. As expected, both primary and secondary resistance to KRASG12C inhibitors invariably occurs, and molecular mechanisms have been characterized in pre-clinical models and patients. Several mechanisms such as tyrosine kinase receptors (RTKs) mediated feedback reactivation of ERK-dependent signaling can result in intrinsic resistance to KRAS target therapy. Acquired resistance to KRASG12C inhibitors include novel KRAS mutations such as Y96D/C and other RAS-MAPK effector protein mutations. This review focuses on the intrinsic and acquired mechanisms of resistance to KRASG12C inhibitors in KRASG12C mutant non-small cell lung cancer and the potential clinical strategies to overcome or prevent it.

scholarly journals Integrating Liquid Biopsy and Radiomics to Monitor Clonal Heterogeneity of EGFR-Positive Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Federico Cucchiara ◽  
Marzia Del Re ◽  
Simona Valleggi ◽  
Chiara Romei ◽  
Iacopo Petrini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Target Therapy ◽  
Case Series ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Clonal Heterogeneity

BackgroundEGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient’s follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.Case presentationIn this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p <0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.ConclusionTo our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.

Coexpression patterns of IDO-1, PD-L1 and EGFR in non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14279-e14279 ◽  
Author(s):  
Weili Wang ◽  
Chen Zhang ◽  
Liang Cheng ◽  
Jianyue Jin ◽  
Feng-Ming Spring Kong
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Expression Patterns ◽  
Small Cell ◽  
Treatment Modalities ◽  
Small Cell Lung ◽  
Indoleamine 2 ◽  
Nsclc Patients

e14279 Background: Indoleamine-2, 3-dioxygenase (IDO), a well-established immune suppressor, may offset efficacy of immune checkpoint inhibitors (ICIs) such as programmed death receptor ligand-1(PD-L1) by inducing unfavorable tumor microenvironment. The unpredictability of one ICI response may partially due to the concomitant presence of other ICIs. Therefore, increasing interest has been focus on the dual ICIs or the combination of ICIs with conventional treatment modalities such as radiotherapy, chemotherapy as well as target therapy. This study aimed to study the coexpression patterns and significance of IDO-1, PD-L1 and epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). Methods: Patients with newly diagnosed NSCLC enrolled in three prospective surgery clinical trials were included in this study. The expressions of IDO-1, PD-L1 and EGFR were evaluated by immunohistochemistry (IHC). For positive cases, the percentile score and H-score were generated respectively from two independent pathologists. The descriptive analysis of Crosstab was used to compare the distributions of these biomarkers expression by pathological types. Results: A total of 117 patients (adenocarcinoma -54%, squamous cell carcinoma -32% and others -14%) with pretreatment tissue specimen available for IHC analysis were studied. Of these, 105 (90%) were from lung primary and 12 (10%) from distant metastasis sites. The expressions of IDO-1 (≥ 1%), PD-L1 ((≥ 1%) and EGFR (≥ 90% or intensity = 3) were identified in 43%, 40% and 52% of NSCLC patients. For IDO-1 and PD-L1, coexpression rates were 21% for co-positive and 37% for co-negative. However, there were still 42% patients showed isolated PD-L1 (20%) or IDO-1 expression (22%). The coexpression rates for EGFR and IDO-1 were 21% for co-positive and 26% for co-negative. The coexpression rates for EGFR and PD-L1 were 20% for co-positive and 25% for co-negative. 38% patients had a positive EGFR with either IDO-1 or PD-L1 positive. The expression patterns were not significant associated with clinical factors including pathological types and differentiation grades. Conclusions: IDO-1 and PD-L1 expression patterns may be useful in the selection of NSCLC patients for dual ICIs immunotherapy. The combinations of EGFR target therapy with immunotherapy may benefit some of NSCLC patients. However, testing expression status of EGFR and immune checkpoints becomes essential since majority of NSCLC patients exhibits EGFR positive with IDO-1 or PD-L1 negative patterns.

scholarly journals MACC-1 antibody target therapy suppresses growth and migration of non-small cell lung cancer

2017 ◽  
Vol 16 (5) ◽  
pp. 7329-7336 ◽  
Author(s):  
Woda Shi ◽  
Jianxiang Song ◽  
Wencai Wang ◽  
Yajun Zhang ◽  
Shiying Zheng
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
And Migration

RET fusion in first/third-generation EGFR-TKIs resistance in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20634-e20634 ◽  
Author(s):  
Yu Yao ◽  
Min Zhang ◽  
Xiuju Liu ◽  
Jun Zhao ◽  
Xiangyang Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Therapy ◽  
Small Cell ◽  
Egfr Mutations ◽  
Third Generation ◽  
Small Cell Lung ◽  
Single Nucleotide Variants ◽  
Egfr Tkis

e20634 Background: EGFR-TKIs is the standard first/second-line treatment for EGFR-mutant advanced non-small-cell lung cancer (NSCLC). The mechanisms of EGFR-TKIs resistance are still under exploration. Acquired fusion have been reported contribute to EGFR-TKIs resistance. Here we focus on RET fusion in first/third-generation EGFR-TKIs resistant NSCLC. Methods: We retrospectively reviewed 3600 cases of EGFR-TKIs resistant NSCLC samples from 2016 to 2018 in our institute. Tumor biopsy, ctDNA or pleural effusion samples were analyzed using hybridization capture-based NGS ER-seq method, which enables simultaneously assess single-nucleotide variants (SNV), insertions/deletions (indel), rearrangements and somatic copy-number(CNV) variation at least 59 genes (range 59-1021 genes). Results: Seven cases with RET fusion were identified (7/3600, 0.2%), with co-occurring EGFR mutations. All were adenocarcinoma, median diagnosis age was 55 years old (range 38-84), four male and three female. Most common RET fusion subtype was CCDC6-RET (5/7, 71%), the other was NCOA4-RET (2/7, 29%). The primary EGFR mutation include four EX19del and three L858R. Six patients received prior first and third-generation EGFR-TKIs treatment. The seventh patient had received only gefitinib treatment, EGFR L858R + T790M + NCOA4-RET were discovered in his plasma when disease progression. Interestingly, one patient had EGFR EX19del + T790M + C797S (cis) + CCDC6-RET in plasma after osimertinib resistance. One patient who had EGFR L858R and NCOA4-RET chose lenvatinib, a RET inhibitor, and had a progression free survival of seven months. Conclusions: Broad NGS panel test suggests that RET fusion could be a rare mechanism of EGFR-TKIs resistance, include first and third-generation. There is no currently target treatment strategy available for these patients, and further investigations, like change target therapy drug or combined target therapy are needed.

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