Publications by authors named "Miao-zhen Qiu"

This phase 2/3 trial (NCT04856787) assessed the efficacy and safety of SHR-1701, a bifunctional protein targeting PD-L1 and TGF-β, in combination with BP102 (a bevacizumab biosimilar) and XELOX (capecitabine plus oxaliplatin) as a first-line treatment for unresectable metastatic colorectal cancer (mCRC). In this phase 2 study, a total of 62 patients with untreated, histologically confirmed colorectal adenocarcinoma and no prior systemic therapy for metastatic disease were enrolled. Patients received SHR-1701 (30 mg/kg), bevacizumab (7.

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HER2-positive gastric cancer has a poor prognosis, with a high incidence of drug resistance and a lack of effective treatments for drug-resistant patients. The exploration of the mechanism of resistance to HER2-targeted therapy in HER2-positive gastric cancer and the identification of effective strategies to reverse it are urgently needed. In this study, we found that HER2-targeted agents upregulated the expression of GSDME and that the overexpression of GSDME attenuated the sensitivity of HER2-targeted agents.

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Background And Purpose: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied.

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Background: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial.

Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS).

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Article Synopsis
  • The study aimed to assess the effectiveness and safety of tislelizumab combined with chemotherapy for advanced gastric cancer compared to a placebo with chemotherapy.
  • Conducted from December 2018 to February 2023 across multiple continents, it involved 1,657 adult patients with specific cancer types who had not previously undergone systemic treatment.
  • Results indicated that patients receiving tislelizumab plus chemotherapy experienced significant improvements in overall survival compared to those on placebo and chemotherapy.
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Background: Immune checkpoint inhibitors are approved for the treatment of various tumors, but the response rate is not satisfactory in certain malignancies. Inhibitor of apoptosis proteins (IAP) ubiquitin-E3 ligase activity is involved in the regulation of immune responses. APG-1387 is a novel second mitochondria-derived activator of caspase (Smac) mimetic IAP inhibitor.

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  • Immune checkpoint inhibitors (ICIs) combined with chemotherapy are effective first-line treatments for metastatic gastric and gastroesophageal adenocarcinomas (GEACs), leading to improved overall survival (OS) and progression-free survival (PFS) when compared to chemotherapy alone.
  • A study analyzed data from six randomized phase III trials involving 5,242 patients, revealing that the optimal combined positive score (CPS) threshold for benefiting from ICIs therapy is ≥5 for OS and ≥10 for PFS.
  • It was concluded that while the effectiveness of ICIs plus chemotherapy is similar across different patient populations, those with lower PD-L1 CPS values (below the suggested thresholds) may not experience significant benefits, highlighting the need
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  • A clinical trial was conducted to compare the effectiveness and safety of two treatments—cetuximab plus FOLFOXIRI (triplet therapy) and cetuximab plus FOLFOX (doublet therapy)—in RAS/BRAF wild-type colorectal cancer patients who had unresectable liver metastases.
  • The study enrolled 146 patients across seven medical centers in China between April 2018 and December 2022, assessing their objective response rate and other outcomes such as tumor response and survival.
  • Results showed that the response rates were similar between the two treatment groups (84.7% for triplet vs. 79.7% for doublet), indicating no significant difference in efficacy, and the trial also monitored
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  • - The CAPability-01 trial studied the effectiveness of combining the PD-1 antibody sintilimab with the HDAC inhibitor chidamide, with or without the VEGF antibody bevacizumab, in patients who have advanced colorectal cancer resistant to chemotherapy.
  • - Results showed that the combination therapy (triplet arm) significantly improved progression-free survival and overall response rates compared to the dual therapy (doublet arm), indicating increased treatment efficacy.
  • - Patients experienced various adverse side effects, with two treatment-related deaths reported; however, the analysis suggested the triplet therapy led to enhanced immune activity in the tumor environment.
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The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer.

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Epstein‒Barr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq.

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Background: Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis.

Methods: HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021.

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  • - Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a complex and aggressive tumor consisting of two types: adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC), but its genetic evolution is not well understood.
  • - Analysis of 101 samples from 33 patients revealed four key mutated genes (TP53, RB1, APC, CTNNB1) and indicated that MANEC tends to have whole-genome doubling, reflecting traits similar to certain other gastric cancers.
  • - The study confirmed that MANEC tumors have a single clonal origin, with NEC components exhibiting more aggressive genetic traits, and it found a sequence of transitions from ACA to NEC, providing new insights into how these tumors
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  • The study focuses on hereditary diffuse gastric cancer (HDGC) and the role of specific genes, particularly CDH1, which accounts for a portion of hereditary cases, while still leaving 50% to 75% of cases unexplained.
  • Researchers conducted a cohort study analyzing genetic samples from 284 HDGC patients in China to assess CDH1 gene alterations and identify potential new susceptibility genes.
  • Results showed a low incidence of CDH1 germline alterations (2.8%) but identified several other genes with higher rates of private germline alterations, suggesting a complex genetic landscape and environmental factors in HDGC.
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Background: SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC).

Patients And Methods: Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD).

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  • PIK3CA mutations are common in solid tumors, making PI3Kα a promising target for cancer treatment.
  • A study tested CYH33, a selective PI3Kα inhibitor, on 51 patients with advanced solid tumors, focusing on safety, maximum tolerated dose, and preliminary efficacy.
  • Results showed a maximum tolerated dose of 40 mg daily, manageable side effects, and a preliminary objective response rate of 14.3% in patients with PIK3CA mutations, suggesting potential effectiveness of CYH33.
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ARX788 is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate with AS269 as cytotoxic payload. In this phase 1 multicenter dose-expansion clinical trial, patients with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment were enrolled. Between July 15, 2019, and March 14, 2022, 30 participants were enrolled.

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  • The study investigated the consistency and prognostic value of tumor regression grade (TRG) compared to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in gastric cancer patients who underwent preoperative treatment.
  • Only 19.6% of patients showed consistent results between the two evaluation methods, indicating a poor agreement between them.
  • TRG was found to be a better predictor of disease-free survival (DFS) and overall survival (OS) than RECIST 1.1, with results showing significant correlations with patient outcomes.
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Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database.

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Importance: The antibody drug conjugate drug MRG003 comprises an anti-epidermal growth factor receptor (EGFR) humanized immunoglobulin G1 monoclonal antibody that is conjugated with monomethyl auristatin E via a valine-citrulline linker. There is currently insufficient evidence of this drug's safety and efficacy.

Objective: To evaluate the safety and maximum tolerated dose of MRG003 in a phase 1a study and investigate the preliminary antitumor activity in EGFR-expressing patients in a phase 1b study.

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Background: Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it.

Methods: The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected.

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  • * A comprehensive analysis of five studies showed that combining PD-1 inhibitors with chemotherapy significantly improves overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in patients.
  • * Among different combinations, Toripalimab with chemotherapy provided the best OS benefits, while patients receiving nivolumab with chemotherapy had the highest ORR; additionally, some combinations exhibited lower severe side effects compared to others.
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Background: Although immune checkpoint inhibitor (ICI) is regarded as a breakthrough in cancer therapy, only a limited fraction of patients benefit from it. Cancer stemness can be the potential culprit in ICI resistance, but direct clinical evidence is lacking.

Methods: Publicly available scRNA-Seq datasets derived from ICI-treated patients were collected and analyzed to elucidate the association between cancer stemness and ICI response.

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Metabolic enzymes have an indispensable role in metabolic reprogramming, and their aberrant expression or activity has been associated with chemosensitivity. Hence, targeting metabolic enzymes remains an attractive approach for treating tumors. However, the influence and regulation of cysteine desulfurase (NFS1), a rate-limiting enzyme in iron-sulfur (Fe-S) cluster biogenesis, in colorectal cancer (CRC) remain elusive.

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