Chemotherapy and targeted therapy are the major treatments for gastric cancer (GC), but drug resistance limits its effectiveness. Here, we profile the proteome of 206 tumor tissues from patients with GC undergoing either chemotherapy or anti-HER2-based therapy. Proteome-based classification reveals four subtypes (G-I–G-IV) related to different clinical and molecular features. MSI-sig high GC patients benefit from docetaxel combination treatment, accompanied by anticancer immune response. Further study reveals patients with high T cell receptor signaling respond to anti-HER2-based therapy; while activation of extracellular matrix/PI3K-AKT pathway impair anti-tumor effect of trastuzumab. We observe CTSE functions as a cell intrinsic enhancer of chemosensitivity of docetaxel, whereas TKTL1 functions as an attenuator. Finally, we develop prognostic models with high accuracy to predict therapeutic response, further validated in an independent validation cohort. This study provides a rich resource for investigating the mechanisms and indicators of chemotherapy and targeted therapy in GC.

The synergistic effect of neoadjuvant immunotherapy and chemoradiotherapy in gastric adenocarcinoma is unclear. This phase II trial (NCT03631615) investigated this neoadjuvant combination in locally advanced adenocarcinoma of stomach or gastroesophageal junction. Thirty-six patients received capecitabine 850 mg/m² twice daily and simultaneous radiotherapy for 5 weeks, sandwiched by a 21-day cycle of oxaliplatin 130 mg/m² (day 1) plus capecitabine 1000 mg/m² twice daily (days 1–14), respectively, followed by surgery. Camrelizumab 200 mg (day 1) was given for 5 cycles since initiating chemotherapy. Primary endpoint was pathological complete response (pCR, ypT0) rate. Secondary endpoints included total pCR (tpCR, ypT0N0) rate, major pathological response (MPR, < 10% residual tumor cells) rate, margin-free (R0) resection rate, downstaging, progression-free survival (PFS), overall survival (OS), and safety. The pCR rate was 33.3% (95% CI, 18.6–51.0), meeting pre-specified endpoint. TpCR, MPR, and R0 resection rates were 33.3%, 44.4%, and 91.7%, respectively. Twenty-eight (77.8%) patients reached ypN0. Two-year PFS and OS rates were 66.9% and 76.1%, respectively. The most common grade 3–4 adverse event was decreased lymphocyte count (27 [75.0%]). Neoadjuvant camrelizumab plus concurrent chemoradiotherapy exhibits promising pathological response in patients with locally advanced gastric adenocarcinoma, with an acceptable safety profile.

Imatinib (IM) has significantly improved the prognosis of gastrointestinal stromal tumor (GIST) patients, but some patients still have primary resistance to IM, and approximately half of patients develop acquired drug resistance within 2 years of treatment, necessitating exploration of new treatment strategies. Targeting ferroptosis as a novel approach to tumor treatment has gained attention. Yet, there is limited research on ferroptosis in GIST, and the underlying mechanism remains unclear. In this study, we revealed that IM increased lipid reactive oxygen species and intracellular Fe²⁺ levels, and decreased glutathione levels in GIST. This effect could be partially inhibited by Ferrostatin-1. Additionally, knocking down STUB1 and overexpressing GPX4 reversed the IM-induced ferroptosis effect. Moreover, STUB1 was identified as a novel E3 ubiquitin ligase of GPX4, promoting the ubiquitination at site K191 of GPX4. The combination of the GPX4 inhibitor RSL3 and IM synergistically induces ferroptosis, inhibiting GIST proliferation both in vivo and in vitro. Furthermore, STUB1 and GPX4 expression serve as independent prognostic factors for GIST. In conclusion, This study is the first to demonstrate that IM induces ferroptosis by promoting STUB1-mediated GPX4 ubiquitination in GIST, and the combination of RSL3 and IM emerges as a promising therapeutic strategy for GIST.

Background: Gastric cancer with synchronous liver metastasis remains a clinical treatment challenge. There has been a longstanding debate on the question whether surgical resection could be beneficial to long-term survival. This study is to investigate the effectiveness and prognostic factors of combined curative resection of the stomach and liver lesions in gastric cancer patients with synchronous liver metastases. Methods: A total of 30 patients who underwent simultaneous curative gastric and liver resection from March 2003 to April 2008 were analyzed retrospectively. Univariate and multivariate analyses were performed to select independent factors for survival. Results: The overall 1-, 2-, 3- and 5-year survival rates of 30 patients were 43.3%, 30.0%, 16.7% and 16.7%, respectively, with a median survival of 11.0 months and 5 patients still living by the time of last follow-up. Single liver metastasis (p = 0.028) and an absence of peritoneal dissemination (p = 0.007) were significantly independent prognostic factors for these gastric cancer patients with synchronous liver metastases. Major adverse events were protracted stomach paralysis in 2 patients and pulmonary infection in another 2 patients, all of whom recovered after conservative treatment. Conclusions: This descriptive study without control group found that patients with solitary liver metastasis and absence of peritoneal dissemination could have better survival benefit from simultaneous curative resection of the gastric cancer and liver metastases.

Inflammatory myofibroblastic tumors are usually treated by surgical resection. We herein report two cases of intra-abdominal inflammatory myofibroblastic tumors that were unresectable and underwent spontaneous regression without any treatment. Our case report and literature review show that regression is more common in the middle-aged and older male populations. Abdominal discomfort and fever were the most common symptoms, but the majority of patients had no obvious physical signs. There was no specific indicator for diagnosis. The majority of the lesions regressed within 3 mo and nearly all of the masses completely resolved within 1 year. We conclude that the clinical characteristics of inflammatory myofibroblastic tumors are variable and, accordingly, the disease needs to be subdivided and treated on an individual basis. Surgery is always the first-line treatment; however, for those masses assessed as unresectable, conservative therapy with intense follow-up should be considered.

The optimal treatment for gastrointestinal stromal tumor (GIST) of the rectum is controversial due to the extremely low incidence of the disease. The aim of the present study was to compare the clinical outcomes of different treatment modalities for rectal GIST by reviewing the 14-year experience in our center. Medical records of rectal GIST patients who received surgical treatment in our center between January 2004 to December 2017 were reviewed retrospectively. Overall survival (OS) and recurrence-free survival (RFS) were used as the observation endpoints. Included in this study were 71 GIST patients, including 42 patients who underwent local excision (LE) and 29 patients who underwent segmental resection (SR). There were differences in tumor size (P = 0.001) and malignant risk grade (P = 0.007). The LE approach achieved a lower rate of R0 resection than SR (29/42 vs.27/29, P = 0.015) and shorter hospital stay (P = 0.004). Preoperative imatinib mesylate (IM) therapy improved the rate of sphincter-sparing surgery for patients with tumors in the very low segment of the rectum (P = 0.012) and offered better R0 resection margins (P = 0.027). Multivariate analysis showed that the resection margin status (P = 0.014), risk stratification (P = 0.001) and IM therapy (P = 0.042) were independent factors affecting RFS of rectal GIST patients but not the surgical modalities (LE vs. SR, P = 0.802). Multivariate analysis showed no significant impact of these variables on OS. Selection of surgical modalities has no significant impact on the prognosis. Local excision is the preferred surgical modality for resectable rectal GIST by virtue of less injury and shorter hospital stay. IM therapy has proved to be associated with improved RFS for rectal GIST patients.