Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

Background: Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD. Methods: All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms “early gastric cancer,” “gastrectomy,” “endoscopic submucosal dissection,” and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model. Results: This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI = 0.41–0.72). Conclusions: Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.

Given the promising outcomes of stereotactic body radiation therapy (SBRT) in treating colorectal cancer liver metastases (CRLMs), we proposed an innovative strategy combining surgery with planned liver SBRT for CRLMs. This retrospective study included patients who underwent curative-intent surgery combined with planned liver SBRT from July 2019 to October 2023. Planned liver SBRT was delivered to residual unresectable and unablatable lesions with maximum diameters of ≤5 cm. Outcomes included local failure (LF), intrahepatic recurrence-free survival (IHRFS), extrahepatic recurrence-free survival (EHRFS), progression-free survival (PFS), overall survival (OS), and radiation-related adverse events. A total of 69 patients were included. The 1-, and 2-year cumulative incidence rates of LF after SBRT were 7.7%, and 9.6%, respectively. The median PFS was 6.2 months, and the median OS was 45.8 months. Multivariate analysis identified RAS/BRAF mutations, extrahepatic metastases excluding lung involvement, and higher CEA as independent predictors of poorer OS. Intrahepatic recurrence was the predominant pattern of first disease progression after combination treatment. Acute grade 1–2 radiation-related adverse events occurred in 56.5% of patients, while grade 3 toxicities were reported in 4.3%. This approach offers favorable long-term outcomes, suggesting its potential to broaden the indications for curative-intent local treatments in CRLMs.