The ubiquitin-proteasome system (UPS) serves as the central mechanism for protein degradation in eukaryotic cells. Deubiquitinases (DUBs), which maintain protein stability and function by removing ubiquitin chains play a key role in protein cycling. Consequently, a DUB-targeting chimera (DUBTAC) technology has emerged. A DUBTAC consists of three components: a protein-targeting ligand, a DUB recruiter, and a linker connecting them. A DUBTAC can simultaneously bind to its targeted protein and DUB and induce the DUB to cleave the ubiquitin chains, thereby restoring the protein function by stabilizing the target protein. The DUBTAC technology provides a novel research strategy involving targeted protein stabilization for conventionally "undruggable" proteins that are abnormally degraded. Compared with other mature technologies, such as proteolysis-targeting chimera (PROTAC) and molecular glue degrader technologies, the DUBTAC technology has the unique advantages of targeting and stabilizing tumor suppressors, thus showing high potential for cancer therapy. However, it is still in the early stage of development with few systematic summaries of recent research achievements. This review introduces the basic concepts, critical design, and research considerations of DUBTACs, summarizes the latest research advances in DUBTAC technology for antitumor drug development, and discusses the development strategies and clinical application prospects of DUBTACs in the future, aiming to provide more directions for research on this technology.

Objective: The optimal adjuvant treatment regimen for pancreatic cancer after surgery remains undetermined. This study aimed to compare the efficacy and safety of S-1 combined with gemcitabine (GS) versus S-1 monotherapy in adjuvant therapy for pancreatic cancer. Methods: A retrospective analysis was conducted on postoperative pancreatic ductal adenocarcinoma (PDAC) patients who received GS or S-1 adjuvant chemotherapy at Peking Union Medical College Hospital from March 2016 to September 2024. Clinicalopathological characteristics, molecular features, treatment details, efficacy outcomes, and toxicity data were collected via electronic medical records and telephone follow-up. Results: A total of 454 patients were included, with 313 receiving GS and 141 receiving S-1. GS-treated patients were generally younger (median age: 62 vs. 66 years, P＜0.001). The median disease-free survival (DFS, 15.4 vs. 12.5 months, P=0.150) and overall survival (OS, 33.5 vs. 24.7 months, P=0.150) showed trends toward prolongation in the GS group compared with the S-1 group. In CA19-9-positive patients prior to adjuvant chemotherapy, GS therapy significantly prolonged DFS (10.7 vs. 8.8 months, P=0.040) and OS (28.2 vs. 19.8 months, P=0.003) compared with S-1 monotherapy. However, the GS group had a higher incidence of grade ≥3 adverse events [59.3%(128/216) vs. 39.4%(26/66), P=0.007], particularly neutropenia [40.7%(88/216) vs. 19.7%(13/66), P=0.003] and fatigue [19.0%(41/216) vs. 7.6%(5/66), P=0.045]. Molecular analysis revealed that TP53 gene variants may predict poor survival outcomes, but no association was observed between homologous recombination repair-related gene variants and treatment efficacy of GS or S-1. Conclusions: GS adjuvant therapy demonstrates trends toward improved DFS and OS compared with S-1 monotherapy in postoperative pancreatic cancer patients, though without statistical significance. GS was superior to S-1 in CA19-9-positive patients. The correlation between genetic mutation profiles and adjuvant treatment outcomes in pancreatic cancer requires further exploration.

To observe the clinical efficacy of herb-spreading moxibustion as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV) of spleen and stomach deficiency cold in gastric cancer.

Objective: To evaluate the safety of neoadjuvant therapy with pembrolizumab combined with 5-fluorouracil (5-FU) and cisplatin in patients with advanced temporal bone squamous cell carcinoma (TBSCC), and its impact on tumor response rate and disease-free survival (DFS). Methods: This prospective, single-arm, open-label clinical study enrolled patients with advanced (Stage Ⅲ/Ⅳ) TBSCC from Sun Yat-sen Memorial Hospital. Patients received 2-3 cycles of neoadjuvant therapy with pembrolizumab, 5-FU, and cisplatin, followed by definitive surgery. Postoperatively, patients received 6 cycles of pembrolizumab combined with radiotherapy. The primary endpoint was the 2-year disease-free survival (DFS) rate. Secondary endpoints included objective response rate (ORR) and safety indicators. Survival analysis was performed using the Kaplan-Meier method. Adverse events (AE) were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Statistical analyses were conducted using SPSS software, version 22.0. Results: From August 2021 to April 2024, 16 patients with advanced TBSCC were enrolled (13 males and 3 females), with a median age of 54 years and a median follow-up time of 2.32 years. Following neoadjuvant therapy, the objective response rate (ORR) was 64.3% (9/14), and the disease control rate (DCR) was 92.9% (13/14). The 2-year DFS rate was 86.6%. Common treatment-related adverse events (TRAE) included leukopenia (56.3%, 9/16), nausea and vomiting (50.0%, 8/16), diarrhea, oral mucositis, and elevated liver function tests (25.0%, 4/16). One patient (6.25%) experienced a grade 3 adverse event. Conclusion: Neoadjuvant pembrolizumab-chemotherapy significantly enhances objective response rate and disease-free survival in advanced TBSCC.

To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment.

Immune checkpoint blockade (ICB) therapy has demonstrated significant efficacy in the treatment of various cancers. However, a subset of patients develops hyper-progressive disease (HPD) following ICB, which is characterized by accelerated tumor growth and poor clinical outcomes. This review outlines the clinical features, potential mechanisms, and possible intervention strategies of HPD, with the aim of informing clinical practice and providing relevant recommendations.
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To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia (AML) cells.

Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis.
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To design a novel bromodomain-containing protein 4 (BRD4) and histone deacetylase (HDAC) dual-target inhibitor (11b), and to elucidate its therapeutic efficacy and mechanisms in suppressing prostate cancer through epigenetic regulation.

Stathmin 1 (STMN1) is a microtubule-binding cytoplasmic phosphoprotein that promotes microtubule depolymerization or inhibits microtubule assembly, thereby regulating cytoskeletal organization and cell cycle progression. STMN1 is upregulated in a variety of malignant tumors, where it drives proliferation, invasion, metastasis, and angiogenesis through classic pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and ferroptosis. STMN1 can also modulate the function of immune cells, thereby influencing antitumor immunity. Clinical data show that its high expression correlates positively with tumor drug resistance and poor prognosis, suggesting that STMN1 has potential as a tumor biomarker and therapeutic molecular target with important clinical significance.

Objective: To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients. Methods: The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected. Results: A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death. Conclusion: BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors.

To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms.

Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.

Immune-related adverse events (irAE) are treatment-associated complications that single or multiple systems could be involved after immune checkpoint inhibitors(ICI), ranging from mild to life-threatening diseases, with significant heterogeneity. This is an important factor which might affect continuous ICI treatment. Patients who have experienced mild to moderate irAE could try ICI rechallenge after they recovered from irAE. However, patients would suffer from same or different irAE during ICI rechallenge. Our patient who was diagnosed with maxillary sinus carcinoma experienced checkpoint inhibitor pneumonitis (CIP) after anti-PD-1 therapy with combined chemotherapy and radiotherapy. Under closely follow-up, he tried same ICI rechallenge. Although he did not suffer from refractory CIP, he was diagnosed with immune-related colitis, which was recovered from ICI discontinuation and treatment of probiotics and Mesalazine.

Objective: To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (T1D). Methods: This was a retrospective case series study of clinical data from 24 patients with ICI-T1D admitted to People's Hospital of Henan Provincial between January 2018 and December 2024. The data collected included demographic characteristics, ICI usage, clinical manifestations, laboratory test results, and clinical outcome. Patients were categorized into mild and severe groups based on disease severity. Clinical characteristics between the two groups were compared using the Mann-Whitney U test. Results: Of the 24 patients, 21 (87.5%) were male and 3 (12.5%) were female, with an average age of (62.0±10.6) years. Patients in the severe disease group were significantly older than those in the mild disease group [(68.0±9.5) years vs. (58.4±9.8) years, P<0.05]. Compared to patients with mild disease, those with severe disease had significantly higher rates of impaired consciousness (9/9 vs.2/15), shorter ICI treatment cycles [3 (2, 6) vs. 6 (5, 8)], shorter time from ICI initiation to diabetes diagnosis [68 (31, 168) d vs. 162 (135, 235) d], and shorter time from the onset of diabetes symptoms to medical consultation [4 (2, 5) d vs. 8 (4, 26) d] (all P<0.05). The severe disease group also showed significantly higher blood glucose levels [43.0 (39.1, 57.3) mmol/L vs. 24.6 (19.6, 29.6) mmol/L] and a lower glycated hemoglobin level [6.8% (6.3%, 7.6%) vs. 7.9% (7.6%, 8.6%)], along with a higher incidence of fulminant T1D (8/9 vs. 2/15, all P<0.05). All patients received insulin injection therapy. After discharge, fasting C-peptide levels in 3 patients with mild disease showed a transient increase to 0.26, 0.43, 0.49 nmol/L but declined again after six months. Conclusions: ICI-T1D is characterized by acute onset and rapid progression. Older patients are more likely to develop severe disease. All patients require insulin therapy.

Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

The clinical data and follow-up outcomes of 9 patients diagnosed with immune checkpoint inhibitor (ICI)-associated myasthenia gravis (MG) admitted to Henan Provincial People's Hospital from January 2021 to October 2024 were collected retrospectively to analyze their clinical characteristics and prognosis. Nine patients were enrolled, including 4 males and 5 females, aged [M (Q1, Q3)] 69 (55, 77) years. All patients had tumors and had received ICI treatment. The time from the start of ICI treatment to the occurrence of MG symptoms or aggravation of the condition was 26 (20, 39) d. Seven patients were classified Myasthenia Gravis Foundation of America Clinical Classification (MGFA) Ⅲ-Ⅴ. All 9 patients had increased creatine kinase and transaminase. Troponin was measured in 5 patients, and all showed elevated levels. ICI therapy was discontinued in all patients at the onset or exacerbation of MG symptoms, and they subsequently received immunomodulatory therapy with pyridostigmine combined with glucocorticoids and/or intravenous immunoglobulin. Symptoms improved in 7 patients and 2 patients showed poor therapeutic effect. The follow-up time was 12.0 (4.5, 16.5) months, and 2 patients died due to the progression of MG superimposed on underlying diseases at the end of the follow-up. ICI-related MG mostly occurs in the early stage of ICI treatment, and is characterized by severe symptoms, rapid progression, and easy complications with myositis/myocarditis. Active initiation of acetylcholinesterase inhibitors combined with immunotherapy can significantly improve outcomes.

Immune checkpoint inhibitor-associated liver injury is a special type of drug-induced liver injury, and its clinical management has already become an emerging topic in recent years. This article focuses on a series of issues that have attracted much attention in the clinical diagnosis and treatment of immune checkpoint inhibitor-associated liver injury, including the clinical type and severity assessment, the role of liver biopsy, differentiation from autoimmune hepatitis, glucocorticoid dose selection, second-line immunosuppressant selection and timing, opportunistic infection prevention, hormone efficacy prediction, and hormone reduction and course of treatment. In addition, this article analyzes the relevant key points and proposes the current issues at the same time that have not yet been resolved, combined with the latest research progress at home and abroad.