Efficacy of immune checkpoint inhibitor rechallenge in initial immunotherapy responders with advanced non-small cell lung cancer: A single-center retrospective study.

Background: The efficacy of immune rechallenge in patients with advanced non-small cell lung cancer (NSCLC) who responded well to initial immune checkpoint inhibitor (ICI) treatment is becoming a research hotspot. This study was aimed at describing the survival and clinical characteristics after immune rechallenge in initial immunotherapy responders.

Patients And Methods: We retrospectively identified 104 patients with advanced NSCLC who responded well in the first ICI and were rechallenged with immunotherapy to treat progression between January 2018 and June 2023 at Zhejiang Cancer Hospital.

New electrophiles targeting thiols in a reversible covalent manner.

Reversible covalent electrophiles with the advantages of both reversible and covalent interactions receive much attention in the fields of chemical biology and medicinal chemistry. Here, we report two electron-deficient olefins activated by amide and ester, amide-substituted acrylamide and methyl ester-substituted acrylamide, targeting thiols in a reversible covalent manner.

Efficacy and Safety of First-Line Platinum-Based Doublet Chemotherapy in Advanced Primary Pulmonary Salivary Gland Tumors (PSGTs).

Primary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain.

Small Molecule-Induced Post-Translational Acetylation of Catalytic Lysine of Kinases in Mammalian Cells.

Reversible lysine acetylation is an important post-translational modification (PTM). This process in cells is typically carried out enzymatically by lysine acetyltransferases and deacetylases. The catalytic lysine in the human kinome is highly conserved and ligandable.

Poor efficacy of immune checkpoint inhibitor treatment in advanced thymic carcinoma patients with liver metastases.

Background: Although immune checkpoint inhibitor treatment for advanced thymic carcinoma exhibits promising efficacy, factors that affect the efficacy and prognosis, including metastases sites, remain uncertain.

Objectives: Our study aimed to investigate the determinants of survival among patients with advanced thymic carcinoma who underwent immunotherapy in real-world settings, with implications for clinical practice.

Designs: Different therapy regimens of immunotherapy were produced to analyze the influence of liver metastases on survival and prognosis for advanced thymic carcinoma patients.

Pyrotinib as a salvage treatment for patients with HER-2 positive advanced lung adenocarcinoma after the progression of afatinib treatment.

Background: The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined.

Method: Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib.

DDCM: A Computational Strategy for Drug Repositioning Based on Support-Vector Regression Algorithm.

Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning.

Assessment of efficacy and safety of MET tyrosine kinase inhibitors in non-small-cell lung cancer patients with MET alterations.

Background: While targeted therapy has become the standard treatment for certain non-small-cell lung cancer (NSCLC) patients with gene mutation positivity, there remains a lack of enough reports of the efficacy of mesenchymal-epithelial transition (MET) alterations in the real world.

Objectives: We aimed to explore the efficacy and toxicity of targeted therapy in NSCLC patients with different types of MET alterations and hope to provide more clinical medication guidance.

Design: Designed different subgroups to compare the efficacy and safety of targeted therapy in NSCLC patients with MET alterations.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

Background: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations.

Methods: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations.

Exploration of efficacy of different therapy regimens for advanced NSCLC patients with KRAS mutation in the first-line treatment.

Purpose: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer.

Methods: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023.

Clinical characteristics and prognostic implications of immune-related hepatitis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a retrospective study.

Background: With the widespread use of immune checkpoint inhibitors (ICIs), patients inevitably experience immune-related adverse events (irAEs). Therefore, the study was conducted on the clinical characteristics and outcomes of patients with non-small cell lung cancer (NSCLC) with immune-related hepatitis (ir-hepatitis).

Methods: We identified patients with advanced NSCLC who developed ir-hepatitis after immunotherapy between June 2016 and December 2022.

Comparison of the efficacy and safety of anlotinib monotherapy or anlotinib plus immune checkpoint inhibitor for advanced small cell lung cancer with brain metastases.

Background: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear.

Method: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified.

Global Reactivity Profiling of the Catalytic Lysine in Human Kinome for Covalent Inhibitor Development.

Advances in targeted covalent inhibitors (TCIs) have been made by using lysine-reactive chemistries. Few aminophiles possessing balanced reactivity/stability for the development of cell-active TCIs are however available. We report herein lysine-reactive activity-based probes (ABPs; 2-14) based on the chemistry of aryl fluorosulfates (ArOSO F) capable of global reactivity profiling of the catalytic lysine in human kinome from mammalian cells.

Efficacy of rechallenge immunotherapy after immune monotherapy resistance in patients with advanced non-small cell lung cancer.

Purpose: Drug resistance inevitably occurs despite the encouraging results of immunotherapy. This study attempted to investigate immunotherapy rechallenge treatment regimens and factors associated with outcomes in patients with non-small cell lung cancer (NSCLC) according to resistance status.

Methods: A retrospective study was conducted on patients with advanced NSCLC who received immune checkpoint inhibitor (ICI) monotherapy and immune rechallenge between March 2016 and December 2022.

Clinical characteristics and prognostic impact of immune checkpoint inhibitor-associated myocarditis in advanced non-small cell lung cancer.

Myocarditis is a rare immune-related adverse events (irAEs) with high mortality rates, with few reports on its clinical characteristics and prognostic impact. This study designed to explore the associations between cardiac parameters and outcomes of myocarditis in advanced non-small cell lung cancer (NSCLC) who treated with immune checkpoint inhibitor (ICI). Fourteen patients diagnosed with ICI-associated myocarditis by clinicians were admitted to the study analysis.

Efficacy and safety of immune checkpoint inhibitors in lung large-cell neuroendocrine carcinoma.

Background: Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare and highly aggressive neuroendocrine tumor. There is currently no standard therapeutic regimen, and systemic chemotherapy results in poor prognosis. Due to the rarity of L-LCNEC, the efficacy and safety of immune checkpoint inhibitors (ICIs) remain unclear.

Comparison of efficacy and safety of second- and third-generation TKIs for non-small-cell lung cancer with uncommon EGFR mutations.

Background: The efficacy of definite for non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations has been preliminarily demonstrated. However, there is a paucity of data with which to compare the efficacy and safety of second- and third-generation TKIs in patients with NSCLC carrying uncommon EGFR mutations.

Methods: We compared the efficacy and safety of second- and third-generation TKIs in all NSCLC patients in whom next-generation sequencing confirmed uncommon EGFR mutations, including G719X, S768I, and L861Q.

Comparison of the immunotherapy efficacy between invasive mucinous and non-mucinous adenocarcinoma in advanced lung cancer patients with KRAS mutation: a retrospective study.

Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma with unique clinical, radiological, and pathological features, among which KRAS mutation is the most common. However, the differences in the efficacy of immunotherapy between KRAS-positive IMA and invasive non-mucinous adenocarcinoma (INMA) patients remain unclear. Patients with KRAS mutated adenocarcinomas receiving immunotherapy between June 2016 and December 2022 were enrolled.

Immune checkpoint inhibitors beyond first-line progression with prior immunotherapy in patients with advanced non-small cell lung cancer.

Background: Immunotherapy, monotherapy, and immunotherapy plus platinum-based chemotherapy are the standard treatments for advanced non-small cell lung cancer (NSCLC) patients with negative driver genes. However, the impact of similar continuing immunotherapy beyond progression (IBP) of first-line immunotherapy for advanced NSCLC has not yet been shown. This study aimed to estimate the impact of immunotherapy beyond first-line progression (IBF) and evaluate the factors associated with second-line efficacity.

Clinical outcomes of immune checkpoint inhibitor therapy for advanced lung adenosquamous carcinoma.

Background: Primary adenosquamous carcinoma (ASC) of the lung is a rare and aggressive disease and limited information is available on the efficacy of immune checkpoint inhibitors (ICIs) for this disease. Here, we evaluated the expression status of programmed death-1 ligand 1 (PD-L1) and efficacy of ICIs in patients with pulmonary ASC.

Methods: The efficacy and toxicity of ICIs were examined in 38 patients with previously treated lung ASC from November 2017 to October 2021 in Zhejiang Cancer Hospital (Hangzhou, China).

Guiding Drug Repositioning for Cancers Based on Drug Similarity Networks.

Drug repositioning aims to discover novel clinical benefits of existing drugs, is an effective way to develop drugs for complex diseases such as cancer and may facilitate the process of traditional drug development. Meanwhile, network-based computational biology approaches, which allow the integration of information from different aspects to understand the relationships between biomolecules, has been successfully applied to drug repurposing. In this work, we developed a new strategy for network-based drug repositioning against cancer.

Concentration-Dependent Enrichment Identifies Primary Protein Targets of Multitarget Bioactive Molecules.

Multitarget bioactive molecules (MBMs) are of increasing importance in drug discovery as they could produce high efficacy and a low chance of resistance. Several advanced approaches of quantitative proteomics were developed to accurately identify the protein targets of MBMs, but little study has been carried out in a sequential manner to identify primary protein targets (PPTs) of MBMs. This set of proteins will first interact with MBMs in the temporal order and play an important role in the mode of action of MBMs, especially when MBMs are at low concentrations.

Efficacy of EGFR-Tyrosine Kinase Inhibitors for advanced non-small cell lung cancer patients harboring rare EGFR mutations of exon 18 E709X.

EGFR-tyrosine kinase inhibitors (TKIs) show efficacy against lung cancer, and afatinib has been used as a standard therapy for patients with non-small cell lung cancer (NSCLC) with EGFR rare mutations such as S768I, G719X, and L861Q. However, the efficacy of EGFR-TKIs against NSCLC with EGFR rare mutations of exon 18 E709X has been less studied. The present study aimed to analyze the efficacy and safety of EGFR-TKIs in NSCLC patients with rare mutations.

Leader gene identification for digestive system cancers based on human subcellular location and cancer-related characteristics in protein-protein interaction networks.

Stomach, liver, and colon cancers are the most common digestive system cancers leading to mortality. Cancer leader genes were identified in the current study as the genes that contribute to tumor initiation and could shed light on the molecular mechanisms in tumorigenesis. An integrated procedure was proposed to identify cancer leader genes based on subcellular location information and cancer-related characteristics considering the effects of nodes on their neighbors in human protein-protein interaction networks.

Cell-Active, Reversible, and Irreversible Covalent Inhibitors That Selectively Target the Catalytic Lysine of BCR-ABL Kinase.

Despite recent interests in developing lysine-targeting covalent inhibitors, no general approach is available to create such compounds. We report herein a general approach to develop cell-active covalent inhibitors of protein kinases by targeting the conserved catalytic lysine residue using key SuFEx and salicylaldehyde-based imine chemistries. We validated the strategy by successfully developing (irreversible and reversible) covalent inhibitors against BCR-ABL kinase.