Project description:Pembrolizumab in metastatic gastric cancer with Mismatch-Repair Deficiency: comprehensive molecular analysis to the clinical response
Project description:Establishment and molecular characterization of 49 peritoneally-metastatic gastric cancer cell lines from 18 patients’ ascites. We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines.
Project description:Molecular characterization of 7 peritoneally-metastatic gastric cancer cell lines and primary cancer cells established from a patients’ ascites. We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines and primary cancer cells.
Project description:Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models that faithfully recapitulate different subtypes of the human disease. To close this gap, we developed methods to somatically introduce different oncogenic lesions directly into the stomach epithelium and show that genotypic configurations observed in patients produce metastatic gastric cancers that recapitulate the histological, molecular, and clinical features of all non-viral molecular subtypes of the human disease. Applying this platform to both wild-type and immune-deficient mice revealed previously unappreciated links between the genotype, organotropism and immune surveillance of metastatic cells that produced distinct patterns of metastasis that were mirrored in patients. Our results establish and credential a highly portable platform for producing autochthonous cancer models with flexible genotypes and host backgrounds, which can unravel mechanisms of gastric tumorigenesis or test new therapeutic concepts aimed at improving outcomes in gastric cancer patients.
Project description:This study was conducted to identify transcriptional profiles predictive of a clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy. Endoscopic biopsy samples were collected from CF-treated metastatic gastric cancer patients prior to therapy and following the development of resistance to therapy.
Project description:Gastric cancer (GC) is a leading cause of cancer-induced mortality with poor prognosis with metastasis. However, the mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches mask roles of subpopulations. To answer questions from the gastric carcinoma intratumoral perspective in the metastasis, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using scRNA-seq. Results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared by a different patient. Clustering data showed significant intratumoral heterogeneity. Results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study we obtained a more comprehensive picture over gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolutionary driving genes (FOS and JUN), which provide a basis for the treatment of heterogeneity.
Project description:This study was conducted to identify transcriptional profiles predictive of a clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy.
Project description:Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease (>50%). Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6- month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control.
Project description:A single arm, Phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, and identify pathologic and transcriptomic correlates of response to therapy.