Background: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs.
Methods: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts.
Background: The efficacy of neoadjuvant treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy in patients with stage III-N2 EGFR-mutant remains unsatisfactory. This study explored the potential benefits of combining first-generation EGFR-TKI with chemotherapy as a neoadjuvant treatment for patients with stage III-N2 EGFR-mutant non-small cell lung cancer (NSCLC).
Patients And Methods: The medical records of patients with III-N2 EGFR-mutant NSCLC who received neoadjuvant therapy with EGFR-TKI at Shanghai Chest Hospital from October 2011 to October 2022 were retrospectively reviewed.
Introduction: The genetic heterogeneity of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor () mutations may affect clinical responses and outcomes to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This study aims to investigate the genomic factors that influence the efficacy and clinical outcomes of first-line, second-line and third-line treatments in NSCLC and explore the heterogeneity of resistance mechanisms.
Materials And Methods: This real-world study comprised 65 patients with mutant NSCLC.
Little is known about the relationship between programmed cell death-ligand 1 (PD-L1) expression and histologic and genetic features in real-world Chinese non-small cell lung cancer patients. From November 2017 to June 2019, tumor tissues were collected from 2674 non-small cell lung cancer patients. PD-L1 expression was detected with immunohistochemistry using the 22C3 and SP263 antibodies, and patients were stratified into subgroups based on a tumor proportion score of 1%, 1% to 49%, and ≥ 50%.
View Article and Find Full Text PDFThe genetic heterogeneity of non-small cell lung cancer (NSCLC) may impact clinical response and outcomes to targeted therapies. In second-line osimertinib treatment for NSCLC, real-world data on genetic biomarkers for treatment efficacy and prognosis remain incomplete. This real-world study involved 68 NSCLC patients receiving first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).
View Article and Find Full Text PDFIntroduction: Durvalumab is a check-point inhibitor against programmed death ligand-1 (PD-L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs.
View Article and Find Full Text PDFObjective: Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC.
Materials And Methods: Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg.
The protein WWOX was reported to be involved in cancer progression via interaction with mTOR and DNA repair pathway. We previously reported noteworthy association of some single nucleotide polymorphisms (SNPs) in mTOR and DNA repair pathways with gastric cancer (GCa) patients' survival. We hypothesized that genetic variants in WWOX gene could predict the survival of GCa patients.
View Article and Find Full Text PDFGenetic improvement of grain quality is more challenging in hybrid rice than in inbred rice due to additional nonadditive effects such as dominance. Here, we describe a pipeline developed for joint analysis of phenotypes, effects, and generations (JPEG). As a demonstration, we analyze 12 grain quality traits of 113 inbred lines (male parents), five tester lines (female parents), and 565 (113×5) of their hybrids.
View Article and Find Full Text PDFBackground: The evidence of combined therapies of multi-target agents in first-line treatment of advanced non-small cell lung cancer (NSCLC) was limited. This study aimed to evaluate the safety and efficacy of anlotinib combined with epidermal growth factor receptor () tyrosine kinase inhibitor (TKI), chemotherapy, or immune checkpoint inhibitor (ICI) in advanced NSCLC.
Methods: This open-label, three-arm, prospective study (NCT03628521) enrolled untreated locally advanced/metastatic NSCLC patients.
Background: Afatinib 30 mg has been proved to be with comparable efficacy but more tolerable than the dose of 40 mg for Asian patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical outcomes of afatinib at 30 mg/d in the treatment of advanced lung adenocarcinomas (LAD) with common and uncommon epidermal growth factor receptor () mutations.
Methods: -mutated advanced LAD patients receiving afatinib (30 mg/d) from January 2017 to November 2021 were retrospectively included.
Background: Dacomitinib is a second-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). ARCHER-1050 showed that this agent can improve progression-free survival and overall survival in advanced non-small cell lung cancer patients with sensitive EGFR mutation compared to gefitinib. However, it is unclear whether dacomitinib is effective in patients with sensitizing uncommon EGFR mutations in exon 18-21.
View Article and Find Full Text PDFRET fusion has emerged as a targetable driver in non-small-cell lung cancer. A comparative analysis on RET fusions at DNA [DNA sequencing (DNA-seq)] and RNA [RNA sequencing (RNA-seq)] levels was performed in this study. Archived tumor samples from 54 non-small-cell lung cancer patients with DNA-level noncanonical RET fusions were selected for RNA-seq.
View Article and Find Full Text PDFBackground: Plant variety identification is the one most important of agricultural systems. Development of DNA marker profiles of released varieties to compare with candidate variety or future variety is required. However, strictly speaking, scientists did not use most existing variety identification techniques for "identification" but for "distinction of a limited number of cultivars," of which generalization ability always not be well estimated.
View Article and Find Full Text PDFIntroduction: It has been well established that Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether Thr790Leu (T790L), which shares the mutation site of Thr790 with Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported.
View Article and Find Full Text PDFBackground: Non-small cell lung cancer (NSCLC) patients harboring mutations in the epidermal growth factor receptor () gene respond dramatically to tyrosine kinase inhibitors (TKIs). However, these patients inevitably develop acquired resistance to -TKIs. Among them, small cell lung cancer (SCLC) transformation is a relatively rare mechanism.
View Article and Find Full Text PDFBackground: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has been considered as an effective treatment in epidermal growth factor receptor-mutant (EGFR-mutant) advanced non-small cell lung cancer (NSCLC). However, most patients develop acquired resistance eventually. Here, we compared and analyzed the genetic alterations between tissue assay and circulating tumor DNA (ctDNA) and further explored the resistance mechanisms after EGFR-TKI treatment.
View Article and Find Full Text PDFTransl Lung Cancer Res
August 2020
Background: Primary or secondary drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) is a new challenge in the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib is a third-generation EGFR-TKI, and its efficacy and safety in NSCLC patients with first-generation EGFR-TKI resistance, especially lung adenocarcinoma, are not yet clear. The purpose of this study was to observe the efficacy and adverse reactions of osimertinib in the treatment of patients with advanced lung adenocarcinoma.
View Article and Find Full Text PDFBackground: Prognosis of patients with stage IIIA-N2 lung adenocarcinoma is still not optimistic. The aim of this study was to evaluate safety, feasibility, and outcomes of surgery after induction epidermal growth factor receptor-tyrosine kinase inhibitor therapy in a clinical trial setting.
Methods: Fourteen patients with IIIA-N2 lung adenocarcinoma and epidermal growth factor receptor mutation received erlotinib induction followed by surgery in a phase II clinical trial.
Background: The optimal neoadjuvant regimen for locally advanced resectable non-small cell lung cancer (NSCLC) remains controversial. EGFR inhibitors have significantly improved survival in patients with -mutant advanced NSCLC. However, their efficacy in neoadjuvant settings, particularly for treating locally advanced NSCLC, remains unclear.
View Article and Find Full Text PDFAnlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non-small cell lung cancer (NSCLC) patients is still elusive. Here, tumor-specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of and genetic profiling.
View Article and Find Full Text PDFBackground: Nowadays, patients with tyrosine kinase inhibitor (-TKI)-sensitive advanced non-small cell lung cancer (NSCLC) receive -TKIs as first-line treatment. We aimed to analyze the relationship between preliminary efficacy (tumor shrinkage within 1 month) and progression-free survival (PFS) after first-line -TKI treatment.
Methods: A total of 82 patients with -TKI-sensitive advanced NSCLC confirmed by histopathology from January 2013 to January 2017 were retrospectively analyzed.
Objectives: To establish a circulating tumor cell (CTC) enrichment system for non-small cell lung cancer (NSCLC) patients who received first-line treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKI), using EGFR magnetic liposomes (EGFR-ML).
Materials And Methods: An inverted evaporation method was used to develop antibody modified EGFR-ML. Peripheral blood was collected from NSCLC patients who underwent first-line EGFR-TKI treatment for CTC enumeration.