Cisplatin remains a cornerstone chemotherapy for many solid tumors but is limited by dose-limiting toxicities, including nephrotoxicity, peripheral neuropathy, and ototoxicity-the latter of which disproportionately affects pediatric patients and lacks effective prevention strategies. Although therapeutic approaches to mitigate cisplatin-induced toxicity are urgently needed, the underlying mechanisms driving organ-specific injury remain incompletely understood. We previously identified apurinic/apyrimidinic endonuclease (APE) 2 as a critical mediator of cisplatin-induced acute kidney injury through disruption of mitochondrial integrity. In this study, we extend these findings to cisplatin-induced hearing loss (C-HL). We demonstrate that cisplatin selectively induces APE2, but not APE1, overexpression in murine and human outer hair cells. Using an inducible, outer hair cell-specific APE2 transgenic mouse model, we show that APE2 overexpression alone is sufficient to cause high-frequency hearing loss, accompanied by hair cell loss and stereocilia disorganization visualized by electron microscopy. Mechanistically, we identified a direct interaction between APE2 and MYH9, mapped the critical MYH9-binding domains, and demonstrated that APE2 knockdown preserved mitochondrial metabolism and protected cochlear cells from cisplatin-induced apoptosis. Notably, APE2 depletion activated an ATR-p53 signaling axis, promoting nuclear p53 localization and suppressing mitochondrial apoptotic pathways. Together, these findings reveal a noncanonical, APE2-dependent mechanism driving C-HL and suggest that targeting APE2 may offer a novel therapeutic strategy to prevent cisplatin-induced ototoxicity.

Frequent drug resistance seriously limits the therapeutic efficacy of sorafenib in advanced hepatocellular carcinoma (HCC). Strategies to increase the response to sorafenib are limited, and the underlying mechanism to facilitate such an increase is not entirely understood. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) expression is high in HCC, promoting the occurrence and progression of HCC. In this study, we explored the mechanism through which HOTAIR knockdown affects the response of HCC cells to the chemotherapeutic sorafenib.

The chick embryo chorioallantoic membrane (CAM) model is gaining increasing attention from cancer researchers worldwide. Its affordability, short experimental duration, robustness, and ease of tumor xenograft visualization make it a valuable tool in cancer research. This review explores recent advancements and potential applications of the avian CAM model, including the following: (1) studying tumor growth and metastasis, (2) investigating mechanisms of tumor chemoresistance, (3) optimizing drug delivery methods, (4) improving bioimaging techniques, (5) evaluating immuno-oncology drug efficacy, (6) examining tumor-extracellular matrix interactions, (7) analyzing tumor angiogenesis, and (8) exploring the roles of microRNAs in cancer. Additionally, we compare the in ovo CAM model with other in vivo animal models and in vitro cell culture systems. Positioned between in vitro and in vivo models in terms of cost-effectiveness and accuracy in cancer recapitulation, the CAM model enhances both preclinical and translational research. Its expanding use in cancer studies and therapy development is expected to continue growing.

The medicinal phytochemical oleandrin (Ole) is obtained from the Nerium oleander plant. The exact relationship between Ole-induced apoptosis and autophagy in gastric cancer (GC) is unclear despite the fact that it has outstanding anti-tumor capabilities. This research aimed to demonstrate how autophagy and Ole-induced apoptosis interact in GC.

Murine double minute 2 (MDM2) is an oncogene that plays a crucial role in regulating the activity of the tumor suppressor protein p53. By binding to p53, MDM2 promotes its degradation, thus promoting the malignant proliferation. The MDM2-p53 interaction has thus generated interest as a therapeutic target, particularly in some sarcomas characterized by the amplification of the MDM2 gene. In this manuscript, we provide an overview of the current and emerging targeted therapies for MDM2-amplified sarcomas.

Trastuzumab resistance remains a challenge for HER2-positive breast cancer treatment. Targeting metabolic reprogramming would provide novel insights for therapeutic strategies. Here, we integrated metabolomics, transcriptomics, and epigenomics data of trastuzumab-sensitive and primary-resistant HER2-positive breast cancer to identify metabolic alterations. Aberrant cysteine metabolism was discovered in trastuzumab primary-resistant breast cancer at both circulating and intracellular levels. The inhibition of SLC7A11 and cysteine starvation could synergize with trastuzumab to induce ferroptosis. Mechanistically, increased H3K4me3 and decreased DNA methylation enhanced SLC7A11 transcription and cystine uptake in trastuzumab-resistant breast cancer. The regulation of epigenetic modifications modulated cysteine metabolism and ferroptosis sensitivity. These results revealed an innovative approach for overcoming trastuzumab resistance by targeting specific amino acid metabolism.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, posing significant therapeutic challenges due to the lack of effective targets. Elevating intracellular calcium levels is a promising strategy in cancer therapy, and highly expressed calreticulin (CALR) in tumors has emerged as a potential target for inducing calcium overload. However, few studies on CALR ligands have been reported. Herein, we designed, synthesized, and evaluated pyrazolopyridine derivatives as potential CALR ligands. Among them, the leading compound 2a was identified as a high binding affinity ligand (Kd = 2.6 μM) with potent antitumor activity (IC50 = 0.1 μM). Mechanistic studies demonstrated that 2a could interact with CALR, inducing calcium overload and leading to apoptosis in TNBC cells. Further in vivo pharmacodynamic evaluations confirmed the safety and antitumor activity of 2a. In conclusion, our findings developed a novel CALR ligand and provided a new anti-TNBC strategy via inducing calcium dysregulation.

Aclarubicin (also called aclacinomycin A) is an antineoplastic from the anthracycline class that is used in China and Japan but not in Europe nor in the USA. Aclarubicin induces much less DNA damage than the classical anthracyclines doxorubicin, daunorubicin, epirubicin, idarubicin, and the anthracene mitoxantrone, but is equally effective in inhibiting DNA-to-RNA transcription and in eliciting immunogenic stress in malignant cells. Accordingly, aclarubicin lacks the DNA damage-associated cardiotoxicity that is dose-limiting for classical anthracyclines. Conversely, aclarubicin is at least as potent as other anthracyclines in inducing immunogenic cell death (ICD), which is key for the mode of action of efficient chemotherapeutics. This combination of reduced toxicity and equivalent ICD-stimulatory activity may explain why, as compared to other anthracyclines, aclarubicin is particularly efficient against acute myeloid leukemia. As a result, we advocate for clinical studies seeking to replace the anthracyclines used in Western medicine by aclarubicin-like compounds. Such clinical studies should not only embrace hematological malignancies but should also concern solid cancers, including those in which ICD-inducing chemotherapies are followed by immunotherapies targeting the PD-1/PD-L1 interaction.

Malignant tumors, as a major challenge in global public health, have posed a significant threat to human life and health. Although traditional chemotherapy can inhibit tumor growth, it is often associated with serious adverse effects and tolerance. Against this background, Chinese medicine therapies have gradually gained wide recognition, and they play an important role in the treatment of gastric cancer (GC). As the core combination of the traditional prescription "Dajianzhong Tang", the medicinal pair of Zanthoxyli Pericarpium and Zingiberis Rhizoma (ZP-ZR) has shown unique advantages in tumor treatment.

Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy; however, the clinical efficacy of anti-PD-1/PD-L1 monotherapy is generally limited, highlighting the need to develop combination therapies. Dogs develop spontaneous tumors in immunocompetent settings, and anti-PD-1/PD-L1 antibodies exert similar clinical benefits. However, no clinically relevant anti-CTLA-4 antibody has been reported, limiting the value of canine tumors as comparative models for human ICI research. Here, canine CTLA-4 was molecularly characterized, and a caninized anti-CTLA-4 antibody (ca1C5) that blocks CTLA-4/ligand binding was developed. Treatment with ca1C5 increased cytokine production in canine immune cell cultures, and the immunostimulatory effect was enhanced when used in combination with the anti-PD-L1 antibody c4G12. As a proof-of-concept, a veterinary clinical study was conducted to demonstrate the safety and clinical efficacy of anti-CTLA-4 antibody as salvage combination therapy in dogs with advanced tumors refractory to prior c4G12 monotherapy. The combination treatment (c4G12 plus ca1C5) was well-tolerated, and evidence of antitumor activity was observed in one dog with oral malignant melanoma. Further studies are warranted to advance veterinary care for dogs and to better characterize canine ICI models for human onco-immunology research.

Immunotherapies targeting the programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) have shown great promise for a subset of patients with non-small cell lung cancer (NSCLC). However, safe and robust combination therapies are still needed to bring the benefit to broader patient populations.

To investigate the potential factors contributing to chemotherapy-related cognitive impairment in elderly lung cancer patients and to offer insights for the creation of an intervention program aimed at enhancing the cognitive abilities of this vulnerable population.

Nanophosphors have gained substantial attention in recent years for both the diagnosis and treatment of cancer. Near-infrared optical imaging based on Nd3+-doped rare-earth nanophosphors is widely used for deep penetration tissue imaging. The present work aims to develop a hierarchical structure of polydopamine (PDA)-coated alginate microspheres encapsulated with NaGdF4@NaYF4:Nd3+ and cisplatin to achieve enhanced photothermal therapy (PTT) alongside providing optical imaging, MRI, and CT multimodal imaging capabilities. The obtained microspheres were subjected to physicochemical characterization, absorption/emission features, radical scavenging potential, drug release, and antibacterial efficacy. Further, the irradiation of microspheres under an 808 nm NIR laser revealed an effective conversion of light energy into a temperature upsurge to 51.3 °C with a conversion efficiency of 53.3%. The hydrophilic NaGdF4@NaYF4:Nd3+ nanophosphors demonstrated significant fluorescence in the NIR range, longitudinal and transverse magnetic resonance relaxivity (r1 = 12.65 mM-1 s-1, r2 = 17.1 mM-1 s-1), and X-ray attenuation capacity of 132 HU. Moreover, cell culture analysis in the presence and absence of NIR irradiation against MG63 cell lines highlights the anticancer potential of the microspheres. These results suggest the potential of prepared microspheres as multifunctional nanotheranostic agents.

Neoadjuvant immunotherapy has shown promising short-term outcomes of perioperative treatments for resectable non-small cell lung cancer (NSCLC) and is expected to release long-term survival benefits. Here, we reported the long-term prognostic value of 18F-FDG PET/CT over ∼a 5-year follow-up.

Polydopamine (PDA) possesses potential as a photothermal agent for tumor treatment owing to its photothermal capacity, chemical modifiability, excellent biocompatibility, and selective biodegradability. However, weak near-infrared (NIR) light absorption seriously hinders its actual utilization, especially in NIR-II. This study presents a novel molecularly modified PDA with remarkably increased NIR absorption and remarkably enhanced photothermal conversion capacity in both NIR-I and NIR-II. Dopamine monomers are covalently bound with elaborately selected 2,6-pyridinedicarboxylic acid (DPA) through an amidation reaction and then undergo an oxidative polymerization to form DPA-doped PDA nanoparticles (DPA-PDA NPs). By constructing donor-acceptor pairs and extending the conjugation length of molecular units, the energy band gap of DPA-PDA between the highest occupied molecular orbital and the lowest unoccupied molecular orbital is diminished from 0.77 to 0.45 eV, facilitating the electron low-energy transition. Meanwhile, the content of carbon-centered free radicals is obviously raised via suppressing their dimerization and quenching by the conjugation effect and steric hindrance effect, where the strengthened electron spin and vibration may promote charge and energy transfers, increasing and accelerating the excited electron nonradiative decay. As a result, the DPA-PDA NPs exhibit the enhanced NIR light absorption (196 and 205% over PDA) and much higher photothermal conversion efficiency (1.4 and 2.1 times that of PDA) under 808 and 1064 nm irradiation, respectively, achieving more effective tumor cells inhibition in vitro and tumor ablation in vivo. Interestingly, photothermal therapies with DPA-PDA for tumor-bearing mice emerge with higher tumor elimination (nearly 100%) under 1064 nm irradiation than that under 808 nm irradiation (94.3%), without recurrence within 20 days, which is attributed to both the enhanced photothermal capacity of DPA-PDA and the stronger tissue penetration ability of NIR-II. This design provides a new option to enhance the photothermal capacity of polydopamine as an applicative photothermal agent for tumor therapy.

Endocrine therapy is an essential treatment to improve disease-free and overall survival in patients with hormone receptor-positive breast cancer. However, symptoms associated with endocrine therapy severely affect patients' quality of life and medication adherence. To inform symptom management strategies, this study systematically reviews research on patients' symptom experiences and coping strategies during endocrine therapy.

Although the programmed cell death protein 1 (PD-1) blockade has been authorized for the treatment of recurrent and metastatic cervical cancer (CC) patients, a significant proportion of CC patients show low objective response rates (ORR) to immune checkpoint blockades (ICBs). Therefore, identifying novel combination treatment strategies to enhance ICBs therapeutic efficacy for CC patients is urgently needed. Here, we discovered that CD39 was highly expressed in exhausted CD8 + T cells from 10 CC patients in our center via single-cell RNA sequencing (scRNA-seq). Furthermore, we validated that CC patients with CD39 highly expressed in CD8 + T cells associated with poor prognosis and immunoevasive subtype of CC both in cohort from our center and the Cancer Genome Atlas (TCGA) database. Moreover, it was also confirmed that CD39-inhibiting not only enhanced the cytotoxicity of CD8 + tumor-infiltrating lymphocytes (TILs) but also promoted the infiltration of B cells through increasing CXCL13 secretion both in vitro experiments and subcutaneous tumor models, thereby amplifying anti-tumor immunity of PD-1 blockade. What was more, we have developed a liposome containing POM-1, which effectively enhanced the anti-tumor effect of POM-1. Our findings provide compelling evidence that targeting CD39 represents a promising "two birds with one stone" strategy for cervical cancer treatment.

Immune-suppressive tumor-associated macrophages (TAMs) that infiltrate the tumor microenvironment (TME), along with the presence of the blood-brain barrier (BBB), influence the effectiveness of immunotherapy for glioblastoma. In this study, we report the use of difluoromethylornithine (DFMO), aPD-L1, and Indocyanine Green (ICG) in combination with target TAMs for their repolarization. DFMO repolarizes TAMs by inhibiting the expression of aconitate decarboxylase 1 (ACOD1), while aPD-L1 blocks the PD-1/PD-L1 immune checkpoint on TAMs, achieving efficient phenotypic switching and enhancing the phagocytic activity against glioblastoma (GBM). When combined with the photothermal agent ICG, the photothermal effect induces immunogenic tumor cell death and further strengthens the repolarization of TAMs. This increases the conversion efficiency of TAMs, reverses immune suppression at the tumor site, and transforms the anti-inflammatory "cold" tumor into a pro-inflammatory "hot" tumor. This approach showed better therapeutic effects in an orthotopic glioma model in mice, with the repolarization of our combined treatment DFMO + N-aP@ICG (nanovesicles containing aPD-L1 and ICG), increasing by 179% compared to other combined treatments for glioma. In summary, we propose this innovative immunotherapy for glioma, which effectively penetrates the blood-brain barrier, targets M2-TAMs, enhances the aPD-L1 immune response, and inhibits the proliferation of glioma.

Fluoxetine, an antidepressant, has shown potential anticancer effects. However, its therapeutic efficacy is limited by its poor bioavailability and rapid metabolism. Nanotechnology is advancing medicine, particularly in developing suitable drug delivery systems to improve therapeutic effects and reduce drug side effects.

Multiple myeloma (MM) ranks second only to lymphoma among hematologic malignancies in terms of incidence. Current treatment methods primarily rely on proteasome inhibitors (PIs) targeting the ubiquitin proteasome system (UPS). However, existing PIs regimens encounter several limitations, including severe adverse effects, rapidly developing resistance during treatment, and restricted therapeutic efficacy. In light of this, our work aims to explore strategies to mitigate poor conditions. We employed a systematic structural optimization process to design and synthesize the new compound BC12-3, based on prevailing PIs. JFCR39 COMPARE analysis was used to assess cytotoxic activity against 39 characteristic cancer cell lines, and the IC50 value of BC12-3 was measured using CCK-8 assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry, while western blotting investigated the antitumor mechanism of BC12-3. In vivo efficacy and safety of BC12-3 and bortezomib (BTZ) were evaluated in the xenograft model. ADMET computational analyses estimated the biological safety of these two inhibitors. As a result, BC12-3 exhibited potent broad-spectrum antitumor activity in vitro particularly against MM cells; This effect was achieved by selectively inhibiting β5 subunit of proteasome activity. BC12-3 suppressed MM cell growth primarily via cell cycle arrest in G2/M phase and apoptosis induction, the related molecular pathways confirmed these phenomena. In vivo studies indicated that BC12-3 exhibits significant effect in inhibiting tumor growth, with its efficacy comparable to that of the standard therapeutic drug, BTZ. Additionally, this new compound showed an excellent safety profile. Consequently, BC12-3 holds promise as a novel therapeutic strategy for the treatment of MM.