Publications by authors named "CaiCun Zhou"

Background: Ivonescimab is a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor, yielding promising clinical outcomes for patients with advanced non-small cell lung cancer in early-phase studies. We compared the efficacy and safety of ivonescimab with pembrolizumab in patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer.

Methods: HARMONi-2 is a randomised, double-blind, phase 3 trial across 55 hospitals in China.

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Accumulation of regulatory T (Treg) cells, an immunosuppressive population, limits the efficacy of immunotherapy in non-small cell lung cancer (NSCLC). C-C Motif Chemokine Receptor 8 (CCR8) is selectively expressed in tumor-infiltrating Treg cells and, thus considered an ideal target. Across four NSCLC-bearing mice models, the combination of CCR8 antibody and programmed cell death protein-1 (PD1) inhibitor significantly reduced tumor growth without obvious mouse body weight drops and systemic cytokine storm.

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Central and peripheral extensive-stage small-cell lung cancer (ES-SCLC) are reported to be two distinct tumor entities, but their responses to the front-line therapies and underlying biological mechanisms remain elusive. In this study, we first compared the outcomes of central and peripheral ES-SCLC receiving front-line chemotherapy or chemo-immunotherapy with a cohort of 265 patients. Then we performed single-cell RNA sequencing (scRNA-seq) on nine treatment-naïve ES-SCLC samples to investigate potential mechanisms underlying the response differences.

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Background: PD-1 blockade plus chemotherapy has become the first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without oncogenic drivers. Oncogenic-driven advanced NSCLC showed limited response to PD-1 blockade monotherapy or chemotherapy alone. Whether NSCLC patients with oncogenic drivers could benefit from PD-1 blockade plus chemotherapy remains undetermined.

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Purpose: Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.

Materials And Methods: 1130 LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME.

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Background: Co-inhibition of immune checkpoints lymphocyte-activation gene 3 (LAG-3) and PD-1 is believed to enhance cancer immunotherapy through synergistic effects. Herein, we evaluate the safety and efficacy of IBI110 (anti-LAG-3 antibody) with sintilimab (an anti-PD-1 antibody) in Chinese patients with advanced solid tumors.

Methods: In this open-label phase I study, phase Ia dose escalation of IBI110 monotherapy and phase Ib combination dose escalation of IBI110 plus sintilimab were conducted in patients with advanced solid tumors.

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Introduction: Pyrotinib, a novel pan-HER tyrosine kinase inhibitor, has demonstrated substantial anti-tumor activity in patients with NSCLC harboring HER2 mutations. Nevertheless, the inevitable resistance to pyrotinib necessitates an in-depth understanding of the underlying mechanisms.

Methods: Resistance-associated mutations were identified through genomic sequencing of paired baseline and post-resistance samples from 40 patients.

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Article Synopsis
  • A phase 3 trial (CHOICE-01) showed that combining toripalimab with chemotherapy significantly improves progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC).
  • The final analysis revealed a median overall survival (OS) of 23.8 months for the toripalimab group compared to 17.0 months for the control group, particularly benefiting non-squamous patients.
  • The study also emphasized the role of circulating tumor DNA (ctDNA) and tissue-based sequencing in identifying biomarkers that predict treatment efficacy, suggesting continuous ctDNA monitoring could enhance personalized treatment strategies.
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  • Third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used to treat patients with EGFR-mutant non-small cell lung cancer (NSCLC), but the factors affecting response or resistance to these treatments remain unclear.
  • This study utilized various advanced techniques such as single-cell RNA sequencing and flow cytometry to analyze tumor samples before and after treatment, revealing that resistant tumors had a significant presence of CXCR1 neutrophils, which were linked to immune suppression and tumor growth.
  • Patients with lower levels of CXCR1 neutrophils prior to treatment had better outcomes, including longer progression-free and overall survival, suggesting that CXCR1 neutrophil infiltration could serve as a predictor for treatment efficacy
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The discovery of the association between EGFR mutations and the efficacy of EGFR tyrosine-kinase inhibitors (TKIs) has revolutionized the treatment paradigm for patients with non-small-cell lung cancer (NSCLC). Currently, third-generation EGFR TKIs, which are often characterized by potent central nervous system penetrance, are the standard-of-care first-line treatment for advanced-stage EGFR-mutant NSCLC. Rational combinations of third-generation EGFR TKIs with anti-angiogenic drugs, chemotherapy, the EGFR-MET bispecific antibody amivantamab or local tumour ablation are being investigated as strategies to delay drug resistance and increase clinical benefit.

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  • A phase 3 study showed that combining camrelizumab with chemotherapy significantly improved progression-free survival in patients with advanced non-squamous non-small-cell lung cancer compared to chemotherapy alone.
  • After 5 years, overall survival rates were 31.2% for those receiving camrelizumab and chemotherapy versus 19.3% for those on chemotherapy alone, indicating a substantial benefit.
  • Patients who completed two years of treatment with camrelizumab had an impressive 5-year overall survival rate of 84.3%, reinforcing its effectiveness and safety as a first-line therapy for this cancer type.
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Background: The anti-angiogenic drugs showed remarkable efficacy in the treatment of lung cancer. Nonetheless, the potential roles of the intra-tumoral immune cell abundances and peripheral blood immunological features in prognosis prediction of patients with advanced lung cancer receiving anti-angiogenesis-based therapies remain unknown. In this study, we aimed to develop an immune-based model for early identification of patients with advanced lung cancer who would benefit from anti-angiogenesis-based therapies.

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  • Current percutaneous transthoracic needle biopsy (PTNB) systems face challenges, prompting the development of a new registration-free navigation system aimed at improving accuracy and efficiency in CT-guided procedures.
  • A study with 98 participants showed this new system achieved an impressive primary biopsy success rate of 98.98% with significantly fewer CT scans and a short procedure time of about 18 minutes.
  • While the system is deemed effective and safe, it did record few adverse events, primarily hemorrhage and pneumothorax, highlighting the importance of monitoring during clinical use.*
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Efficacious strategies for early detection of lung cancer metastasis are of significance for improving the survival of lung cancer patients. Here we show the marker genes and serum secretome foreshadowing the lung cancer site-specific metastasis through dynamic network biomarker (DNB) algorithm, utilizing two clinical cohorts of four major types of lung cancer distant metastases, with single-cell RNA sequencing (scRNA-seq) of primary lesions and liquid chromatography-mass spectrometry data of sera. Also, we locate the intermediate status of cancer cells, along with its gene signatures, in each metastatic state trajectory that cancer cells at this stage still have no specific organotropism.

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Importance: Patients with extensive-stage small cell lung cancer (ES-SCLC) have poor prognoses and unmet medical needs.

Objective: To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.

Design, Setting, And Participants: This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China.

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  • Oncogenic RET alterations are key targets in various cancers, leading to a phase 1 study of the RET inhibitor SY-5007 in patients with RET-altered solid tumors, focusing on safety, maximum tolerated dose, and efficacy.
  • The study involved 122 patients across different cancer types, revealing a high rate of treatment-related adverse events (96.7%), particularly hypertension and diarrhea, alongside a promising overall response rate of 57.8%.
  • SY-5007 demonstrated notable efficacy regardless of prior treatments, with median progression-free survival of 21.1 months; circulating tumor DNA analysis indicated that monitoring RET alterations could inform treatment responses and resistance.
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  • Anti-PD-1 immunotherapy combined with chemotherapy has been shown to significantly extend survival rates for patients with squamous cell lung cancer (LUSC), but further research is needed to identify predictive biomarkers for treatment response.
  • The study involved RNA sequencing of 349 LUSC samples and additional experiments, revealing that a high presence of activated CD8 T and CD56 natural killer (NK) cells correlates with better patient outcomes.
  • Researchers established a new classification system based on tumor cornification and immune cell infiltration, which could help predict the effectiveness of the combination treatment and highlight potential immune evasion mechanisms in certain tumor cells.
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Introduction: Previous results from the phase 3 ALESIA study (NCT02838420) revealed that alectinib (a central nervous system [CNS]-active, ALK inhibitor) had clinical benefits in treatment-naïve Asian patients with advanced -positive NSCLC, consistent with the global ALEX study. We present updated data after more than or equal to 5 years of follow-up from the "last patient in" date.

Methods: Adult patients with treatment-naïve, advanced -positive NSCLC from mainland China, South Korea, and Thailand were randomized 2:1 to receive twice-daily 600 mg alectinib (n = 125) or 250 mg crizotinib (n = 62).

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Article Synopsis
  • Research seeks to improve chemotherapy and PD-1 inhibitors for advanced non-small-cell lung cancer (NSCLC) by analyzing circulating tumor DNA (ctDNA) from 460 patients in the CHOICE-01 study.
  • Key predictive markers such as ctDNA status, tumor mutational burden, and chromosomal instability were identified to tailor treatment strategies for better patient outcomes.
  • An integrated ctDNA-based stratification system, called blood-based genomic immune subtypes (bGIS), offers a new way to personalize therapies and monitor treatment responses in advanced NSCLC patients.
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