Immune checkpoint inhibitors (ICIs) have become an important part of malignant tumor therapy. However, some adverse reactions follow ICIs therapy. The incidence of immune-mediated colitis (IMC) has also increased. Here, the case of a 67-year-old male patient with stage IVB esophagogastric junction squamous cell carcinoma after chemotherapy, targeted therapy and immunotherapy is presented. This patient underwent treatment with six courses of protein-bound paclitaxel + cis-platinum+ sintilimab, followed by maintenance therapy with sintilimab alone. The patient developed intestinal obstruction, abdominal pain, hemorrhage of the lower digestive tract and other discomfort and was diagnosed with multiple jejunal ulcers via colonoscopy and pathological biopsy. The aims of presenting this case report are to improve clinicians' understanding of and ability to treat sintilimab-related adverse reactions and to more scientifically and rationally administer sintilimab for the treatment of malignant tumors.

To evaluate the short-term efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with hepatocellular carcinoma (HCC) complicated by high-flow hepatic arteriovenous fistula (HAVF).

The emergence of immune checkpoint inhibitors (ICIs) have provided a new perspective for cancer immunotherapy. Immune checkpoint inhibitors significantly improve the survival prognosis of patients with various advanced cancers by inhibiting immune checkpoint molecules, thereby releasing the suppression of T cells by tumor microenvironment, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitor (ICI) therapy, while effective, gives rise to distinct immune-related adverse events (irAEs), including cardiovascular toxicities, necessitating focused research efforts to better understand and address these specific complications. The myocarditis-associated toxicity has been extensively studied. This article reviews the latest clinical and preclinical literature on the epidemiology and pathogenesis of ICI-related atherosclerosis, explores the pathophysiological mechanisms by which ICIs promote atherosclerosis, and discusses risk assessment, identification and monitoring methods, and intervention strategies for ICI treatment related atherosclerosis.

Metal ion-based combination therapy holds great promise for cancer treatment. However, current codelivery systems often suffer from poor biocompatibility-associated severe side effects. Inspired by natural biomineralization processes, we developed biomineralized albumin-macrocyclic conjugates (BAMC) as a codelivery platform for metal sulfides and small-molecule drugs. In this system, bovine serum albumin (BSA) guides the biomineralization of metal sulfides, while surface-conjugated sulfonate azocalix[4]arenes (SAC4A) enable the precise loading of small-molecule therapeutics. Upon reaching tumor tissues, SAC4A is enzymatically degraded and the metal sulfides are converted into bioactive ions, enabling the simultaneous release of therapeutic agents. Using this strategy, BAMC enabled the codelivery of Cu2+ and an HSP90 inhibitor (BIIB021), as well as Zn2+ and an autophagy inhibitor (hydroxychloroquine, HCQ), leading to efficient combination photothermal therapy and cancer immunotherapy in 4T1 tumor-bearing mice. Given the broad applicability of biomineralization techniques to various metal ions and the wide-ranging inclusion capabilities of SAC4A for different drugs, BAMC represents a promising platform for metal ion-based combination therapies.

Distress and physical symptoms are ongoing for early-stage breast cancer survivors on adjuvant hormone therapy. While previous qualitative research has focused on reporting the outcomes of distress and symptoms, as well as medication adherence, this study aimed to understand the link between symptoms and distress, exploring specifically how symptoms are distressing to inform interventions.

With their remarkable activation efficiency, cGAS-STING agonists have emerged as a promising strategy to promote immunotherapy. However, continuous activation of the STING pathway may induce resistance and immune evasion, thus impairing the therapeutic effect. Considering repetitive transient rest could restore immune system function and avoid side effects, here we develop an intermittent STING agonist to reversibly activate the cGAS-STING pathway with "stimulation-suspension" patterns, which induce repetitive "activation-rest" intervals in immunotherapy with enhanced efficiency. Near infrared (NIR) switchable reversible DNA shutter (NIR-DNA shutter), as the intermittent STING agonist, is synthesized by conjugating a pair of segmented complementary DNA strands that incorporated Azobenzene (Azo) to the surface of upconversion nanoparticles (UCNPs). Low power 808 nm irradiation generates a high Vis/UV ratio for UCNPs upconversion emission, which induces trans-Azo isomerization and assembles dsDNA chain along UCNPs surface to activate STING pathway, while high power 808 nm irradiation generates a high UV/Vis ratio for UCNPs upconversion emission, which induces cis-Azo isomerization and disassembles dsDNA chain to pause STING pathway. Switching NIR irradiation powers reversibly converts the NIR-DNA shutter between "ON/OFF" statuses and programs the cGAS-STING pathway with repetitive "activation-rest" interval mode, which demonstrates superior therapeutic efficacy by remodeling the immune-environment and enhancing tumor cell killing compared with the constant STING agonist.

One of the biggest causes of death around the world is cancer. Despite the development of a variety of chemotherapeutic drugs that stop excessive cell division, drug resistance remains a major obstacle to chemotherapy. It is consequently critical to develop and find new and effective anti-cancer agents in order to address the global threat. Owing to coumarins are a promising scaffold for anticancer agents, in this approach, we interested to synthesis new coumarins linked to either 1,3-thiazols or 1,3,4-thiadiazoles and examined their cytotoxic efficacy. Eleven of the newly prepared compounds were selected for the in vitro anticancer investigations against 60 human cancer cell lines at a single dose (10- 5M). Based on the results, we observed that compounds 3a, 3b, 6, 8a, b and 10b were the most active towards different cancer cell lines where the growth inhibition percent (GIP) was up to 96%. Moreover, compound 6 had lethality effect against melanoma MDA-MB-435 and renal cancer A498 with growth percent - 47.47 and - 6.20. Also, the lethal effects were seen with compound 10b where it exerted a value of - 27.79% toward melanoma MDA-MB-435.The highest GIP values 96.03% was recorded for compound 10a against melanoma MDA-MB-435 cancer cell line.

"Glutamine addiction" is a hallmark metabolic feature of many cancer cells. Driven by the "Warburg effect," tumor cells exhibit an increased reliance on glutamine uptake and metabolism to sustain rapid proliferation and survival. As such, precise modulation of glutamine metabolic pathways has emerged as a promising strategy for cancer therapy. Alanine - serine - cysteine transporter 2 (ASCT2), a key glutamine transporter, is frequently overexpressed in a variety of cancer cells, facilitating elevated glutamine influx to meet the metabolic demands of malignant cells. Accordingly, pharmacological inhibition of ASCT2 represents an attractive approach to reduce intracellular glutamine availability and suppress tumor cell growth. This review provides a comprehensive overview of ASCT2, including its structural and functional characteristics, recent progress in small-molecule inhibitor development, and the potential for future therapeutic applications.

Nobiletin, a major component derived from the natural product Citrus reticulata Blanco, has been shown to exhibit potent anti-cancer activity across various cancer types. However, the mechanisms underlying its anti-breast cancer effects, particularly in triple-negative breast cancer (TNBC), remain poorly understood.

Enfortumab vedotin (EV), a novel antibody-drug conjugate directed against Nectin-4, was explored in patients with non-small cell lung cancer (NSCLC) in cohorts 3 and 4 of the open-label, multicohort, Phase 2 EV-202 study (NCT04225117).

Breast cancer is the most common cancer and the main cause of death because of malignant tumors in women, worldwide. The impact of Crocus sativus on several cancers has been discussed. Recent studies provide evidence regarding the anticancer properties of C. sativus and its bioactive constituents against breast cancer. This study aims to systematically review the efficacy of this botanical drug and its constituents on breast cancer, and their mechanism of action for the first time. Due to the lack of human studies in this field, the present research focused on preclinical studies.

This trial evaluated the efficacy and safety of anti-programmed cell death 1 antibody (SCT-I10A) and anti-epidermal growth factor receptor (EGFR) antibody (SCT200) in patients with previously treated advanced esophageal squamous cell carcinoma (ESCC) (trial registration number: NCT04229537).

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype associated with the highest mortality rate among all breast cancer subtypes, primarily due to the absence of actionable therapeutic targets. Although poly (ADP-ribose) polymerase inhibitors (PARPi) have shown promising therapeutic effects in TNBC patients harboring homologous recombination deficiency (HRD), their clinical benefit remains limited, highlighting an urgent need for novel targets that enhance PARPi efficacy. This study investigates the role of Jab1 in regulating the stability of homologous recombination repair (HRR)-related RNAs and evaluates its potential as a therapeutic target to enhance PARPi sensitivity in TNBC.

With a poor prognosis and dynamic invasiveness, gliomas persist as one of the elusive targets in modern oncology, catalyzing a shift in focus towards natural product-based anti-glioma candidates that prioritize therapeutic precision with minimal toxicity. In a previous study conducted in our laboratory, treatment of the Drosophila brain tumor mutant, lethal (2) giant larvae [l(2)gl] with candidate drugs artemisinin and curcumin restored brain architecture, though pupal lethality persisted. Here, we investigate a key artemisinin derivative, dihydroartemisinin (DHA), using the Drosophila l(2)gl/l(2)gl loss-of-function mutant. DHA administration completely rescued the tumor phenotype in the brain and the wing discs in the Drosophila glioma model, improving survival. The behavioral assay conducted to correlate tumor suppression with the restoration of brain function demonstrated restored locomotory abilities comparable to those of the wild-type strain. DHA restored the wild-type cellular architecture in the optic lobes from a spatially disrupted state and transiently elevated reactive oxygen species to suprathreshold levels, suggesting an oxidative stress-mediated anti-oncogenic mechanism. Our work elucidated the therapeutic potential of DHA in vivo in Drosophila and opens up new avenues for further clinical validation with mammalian models and probing into the cellular networks involved in developing effective treatment strategies against glioma.

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by enhancing anti-tumor immune responses, yet their use can lead to immune-related adverse events (irAE), including neurological complications. Despite their clinical relevance, predictive biomarkers for irAE remain scarce, and early identification of at-risk patients is a major unmet need. In this prospective study, 200 patients undergoing ICI therapy were enrolled, of whom 59 underwent longitudinal metabolomic profiling at baseline, three months, and six months. Thirty-two patients who developed irAE were compared to 27 age- and sex-matched individuals without irAE. Multivariate analyses, including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA), revealed distinct metabolomic signatures differentiating the two groups. Notably, baseline levels of triglyceride 20:0_34:1 were significantly lower in irAE(+) patients. In female patients, additional triglyceride species-20:1_34:2, 20:2_34:2, and 20:2_34:3-were also reduced prior to therapy and showed increases within three months of ICI initiation. These findings suggest that specific triglyceride species may serve as early biomarkers for irAE risk, particularly in female patients. The observed dynamic changes point to a potential link between lipid metabolism and immune-related toxicity, supporting the integration of metabolomic profiling into future strategies for risk stratification and personalized monitoring in cancer immunotherapy.

Tumor metastasis constitutes a major obstacle in cancer treatment and affects patients' quality of life. In this study, we synthesized FeIII-shikonin nanoparticles (SF NPs) through a one-step self-assembly process utilizing shikonin (SK) and FeIII. Following the synthesis of nanoparticles, the challenges associated with the poor water solubility and the low bioavailability of SK, as well as its toxicity and adverse effects on normal tissues, could be addressed, thereby enhancing its applicability. Additionally, the synergistic effect between SK and FeIII could be achieved. These nanoparticles were subsequently modified with sodium hyaluronate (HA) to obtain tumor-targeted HSF NPs, characterized by a particle size of 171.2 nm and a zeta potential of -39.85 mV. SK could reduce LA production to improve the tumor microenvironment by downregulating PKM2 activity. Additionally, SK has been observed to downregulate MMP9 expression, resulting in decreased tumor metastasis. The exposure of tumor cells to SK and FeIII induced ferroptosis by disrupting iron ion balance and redox homeostasis. In vivo antitumor activity assessments in CT26-bearing mice demonstrated that the HSF NPs achieved a tumor growth inhibition rate of 76.94 %. By integrating these therapeutic mechanisms, HSF NPs effectively inhibited the growth of orthotopic tumors and the dissemination of metastatic tumors.

Uterine sarcoma is an extremely malignant gynecological tumor, characterized by rapid growth, early metastasis, and a high recurrence rate. Current treatments like surgery, radiotherapy, and chemotherapy, have limited effectiveness, highlighting the urgent need for innovative noninvasive alternatives. Here, we report a novel photosensitive nanocomposite hydrogel (O1-M&F) designed for NIR-induced photothermal therapy (PTT), comprising mildly oxidized MXene (O1-M) and a thermosensitive Pluronic F127 hydrogel. Unlike conventional approaches that aim to prevent MXene oxidation, we demonstrate that mild oxidation significantly enhances both the photothermal conversion efficiency and reactive oxygen species (ROS) generation of MXene nanosheets. The incorporation of F127 hydrogel further ensures the long-term dispersion stability and biocompatibility of the composite system. In vitro and in vivo studies demonstrated potent tumor ablation capability with minimal side effects. Increased apoptosis of uterine sarcoma cells was further observed. The biocompatibility of the O1-M&F hydrogel was validated, indicating its potential for safe and effective therapeutic application. These findings suggest that O1-M&F-based PTT is a promising, noninvasive, effective treatment for uterine sarcoma, offering a novel therapeutic approach with reduced risks and enhanced patient outcomes.

Gastric cancers are classified into four molecular subtypes according to The Cancer Genome Atlas (TCGA) classification: Epstein-Barr virus-positive (EBV-positive), microsatellite instability-high (MSI-H), chromosomal instability (CIN), and genomically stable (GS). Unlike MSI-H gastric cancer, GS and CIN subtypes exhibit immunologically inert microenvironments and demonstrate minimal response to immune checkpoint blockade (ICB), necessitating novel strategies to overcome immunotherapy resistance.

Harringtonine (HT), derived from the genus Cephalotaxus, has demonstrated anti-proliferative effects against non-small cell lung cancer (NSCLC). 5-Fluorouracil (5-FU), a cost-effective chemotherapy, faces resistance issues in NSCLC. Thus, exploring HT's mechanisms in inhibiting NSCLC proliferation and overcoming 5-FU resistance is clinically important.

Proteolysis-targeting chimeras (PROTACs) are an emerging class of therapeutic agents for anticancer treatments by degrading intracellular proteins via the ubiquitin-proteasome system. However, clinical applications of PROTACs are limited by the undesired normal cell toxicity resulting from off-tissue on-target degradation. To address this, we developed a tumor-selective delivery strategy by conjugating carbohydrate moieties to the ligand of the VHL E3 ubiquitin ligase, which enables targeted degradation of proteins of interest in GLUTs-overexpressing cancer cells. We designed and synthesized two series of carbohydrate and BRD PROTAC (ARV-771) conjugates. These compounds degraded BRD4 in a concentration- and time-dependent manner, with NG-2 showing the highest degradation efficiency. Moreover, NG-2's degradation effect was GLUTs- and proteasome-dependent, with selective targeting and effective degradation in high GLUTs-expressing cells. Furthermore, NG-2 inhibited tumor growth without significant toxicity in vivo. These findings demonstrate the potential of carbohydrate-PROTAC as a targeted cancer therapy with minimized off-tissue on-target degradation.