Recent clinical trials have demonstrated that neoadjuvant administration of PD-1 + /- CTLA-4 inhibitor is superior to adjuvant PD-1 inhibitors in patients with resectable stage III and IV cutaneous melanoma. However, the generalizability of these results to an unselected patient population treated in routine clinical settings remains unclear.

Ponicidin, a diterpenoid derived from Rabdosia rubescens, exhibits potent antitumor activity. However, its mechanisms against esophageal squamous cell carcinoma (ESCC) remain obscure. This study aims to explore the effects of ponicidin against ESCC and reveal its molecular mechanisms.

Despite the use of therapeutic modalities such as surgery, chemotherapy, and radiotherapy, breast cancer remains a potentially fatal condition for humans. The primary problems with these treatments are their low efficacy and their inevitable side effects to the surrounding healthy tissues. Overcoming these challenges has been achieved through precision therapeutics, where personalized interventions have significantly improved treatment efficacy. However, the development of nanoparticles has largely remained focused on optimizing delivery platforms based on a one-size-fits-all approach. As lipid-based, polymeric, and inorganic nanoparticles are now being engineered with greater specificity, they are increasingly suited for customization-paving the way for truly personalized drug delivery in the era of precision medicine. In this line, the current study focuses on breast cancer, and recent developments in drug delivery. The first part of this review looks at practical difference between precision medicine and precision targeting. It describes breast cancer signaling pathways, highlighting the exciting potential of nanotechnology in cancer drug delivery using precision targeting - an approach closely linked to precision medicine. We also go over how nanostructures can improve the way drugs, genes, and immunotherapy are delivered in the treatment of breast cancer. Lastly, we discuss challenges, solutions, future directions, and possibilities for the practical use of nanotechnology in the treatment of breast cancer, while introducing nano-products based on clinical trials.

An interesting sunlight-driven photodynamic therapy (PDT) has been realized. In this study, we propose a strategy involving an intramolecular electron-donating ligand to develop a high-performance type-I photosensitizer. Specifically, an electron-rich core is flanked by two iridium atoms, facilitating electron transfer and promoting hydroxyl radical generation. The resulting Ir(III) photosensitizer, Q-T, boosts the rapid generation of reactive oxygen species (ROS) under low-intensity laser exposure. Moreover, the type-I ROS ideally suits hypoxic microenvironments, thus demonstrating remarkable PDT against various cell lines, under artificial and natural sunlight. In a skin squamous carcinoma (A431) organoid model, one cycle of treatment of dosing of Q-T followed by sunlight irradiation effectively induces cellular apoptosis and completely eradicates tumor organoids. This approach offers a promising avenue for the efficient PDT of skin cancer utilizing sunlight.

Older adults with advanced cancer are at risk for toxicities and declines in physical function, which can impact their ability to perform instrumental activities of daily living (IADLs, e.g., preparing meals, managing medications, and cleaning). This decline is a key predictor of treatment outcomes and survival in this population. To address this, we conducted a two-arm, randomized trial to evaluate the feasibility of a home-based chair exercise intervention (ChairEx), delivered in-clinic by oncology staff.

Epidermal growth factor receptor inhibitors (EGFRIs) and immune checkpoint inhibitors (ICIs) show promising efficacy in colorectal cancer and head and neck squamous cell carcinoma therapy, especially in combination. However, given the many cutaneous adverse effects (CAE) associated with each, there is concern for overlap and exacerbation of toxicities. EGFRIs are associated with acneiform rashes and paronychia, while ICIs are associated with lichenoid dermatitis and psoriasis. Xerosis, pruritus, and eczema are seen with both drugs. Understanding the CAEs of EGFRI-ICI combination therapy may guide the management of toxicities and improve adherence to life-saving therapy.

The pathogenesis of uterine carcinosarcoma (UCS) remains unclear due to a few mature cell lines. Herein, we established a new cell line, ESCA, from a Chinese woman. Especially, three sublines, named ESCA-2, ESCA-3, ESCA-5, were isolated based on the rate of cells' different sedimentation. All ESCA cells have been subcultured for more than 60 generations. ESCA sublines display different cell morphology and growth characteristics, as well as have different sensitivity to chemotherapeutic drugs. ESCA was most sensitive to paclitaxel and carboplatin, while ESCA-2 was most sensitive to ifosfamide. Besides, ESCA showed severe chromosome karyotype abnormalities and abnormal number of chromosomes. Whole exome sequence showed ESCA and its sublines, as well as tissue block shared similar single nucleotide variants, such as TP53, TRRAP mutations, while relatively large differences in mutational signature abundance. When all ESCA cells were xenotransplanted subcutaneously into BALB/c-nu mice, they developed into tumors that resembled the original tumor with positive AE1/3 and Vimentin in immunohistochemical staining. Interestingly, the transplanted tumor from ESCA-5 proliferated fastest with a relatively low level of glucose uptake evaluated by micro-PET/CT scanning. Taken together, ESCA and its sublines may be valuable tools to explore the molecular mechanism of UCS.

Anti-HER2 monoclonal antibody (mAb) is the standard first-line therapy for advanced HER2+ gastric cancer. However, resistance to anti-HER2 therapy remains a significant clinical challenge. In this study, we identified a novel resistance mechanism to anti-HER2 therapy in gastric cancer and proposed a strategy to enhance therapeutic efficacy by activating T cells. The association between intratumoral immune cells and clinical responses to anti-HER2 therapy in gastric cancer was investigated. Peripheral blood mononuclear cells (PBMCs) were co-cultured with HER2+ gastric cancer cell lines or organoids to study NK cell responses mediated by anti-HER2 mAb. T cells were depleted or activated to assess their impact on antibody-dependent cellular cytotoxicity (ADCC), and the mechanism by which T cells influence ADCC was examined. The combinatorial effects of anti-HER2 mAb and HER2 × CD3 T cell-engaging bispecific antibody (bsAb) in gastric cancer were evaluated. A total of 35 gastric cancer patients receiving anti-HER2 mAb treatment were enrolled. A higher number of intratumoral T cells were associated with greater tumor regression and improved overall survival following anti-HER2 mAb therapy. Mechanistically, T cells, mainly CD4+ T cells, influence NK cell functional and phenotypic changes via interleukin-2 (IL-2) production. Activating T cells by HER2 × CD3 T cell-engaging bsAb enhanced the anti-tumor effects of anti-HER2 mAb in gastric cancer. Our study identified the lack of T cell help as a novel resistance mechanism to anti-HER2 mAb in gastric cancer. Enhancing T cell help via the combination of HER2 × CD3 bsAb improved the therapeutic efficacy of anti-HER2 mAb in gastric cancer.

The side effects and resistance to treatments associated with platinum compounds, such as cisplatin, underscore the present need for novel anticancer agents with improved properties. The development of hybrid drugs, combining two bioactive units, offers a promising approach by synergistically enhancing the biological activity of the two fragments while reducing the resistance of classic drugs. This work presents the synthesis of a novel family of heterobimetallic compounds, featuring a monofunctional Pt(II) complex with amino groups and a p-ferrocenylaniline ligand. Cytotoxic assays reveal that the derivatives with methylated and isopropylated substituted amines exhibit remarkably higher activity against several tumor cell lines compared with cisplatin and the unsubstituted diamino complex. Notably, these methylated and isopropylated complexes demonstrate high selectivity and present high antitumor activity in cell lines where cisplatin is ineffective. Classical molecular dynamics simulations targeting DNA reveal a consistent relation between the extent of distortion of the duplex upon complex coordination and the cytotoxic activity observed in biological assays. According to our simulations, coordination of the heterometallic complexes can produce a significant disruption of the H-bond pattern of the platinated guanine. Moreover, the distortion mechanism induced by the voluminous substituents of the amino ligands entails either the intercalation of the ferrocene moiety, facilitating new hydrogen bonds between originally non-interacting base pairs and new weak attractive stacking interactions between the Pt(II) complex and neighboring nucleobases, or the displacement of adjacent nucleotides from the pairing region toward the solvent environment.

This study aims to evaluate the efficacy of compression therapy in preventing oxaliplatin-induced peripheral neuropathy (OIPN) in colorectal cancer patients.

Immunotherapy is an emerging and effective treatment for cancer. The mRNA-based cancer vaccines enhance the immune response to cancer cells by activating T cells. However, the cytotoxic T-lymphocyte antigen (CTLA-4) receptor signaling inhibits T-cell activation, thereby reducing the effectiveness of the mRNA-based vaccines. Fortunately, the anti-CTLA-4 monoclonal antibody therapy can block CTLA-4 signaling. Nevertheless, the use of anti-CTLA-4 antibodies is also accompanied by immunotoxic side effects. Therefore, an effective and safe medication regimen plays an essential role in the treatment of cancer. First, we develop a mathematical model to describe the interaction of mRNA-based cancer vaccines and anti-CTLA-4 antibodies under the tumor immune microenvironment. Secondly, by employing the method of Markov Chain Monte Carlo (MCMC), the model is parameterized using experimental data, and the simulations are in agreement with experimental results. Finally, the gradient descent method is designed to optimize the medication regimens to inhibit tumor growth and reduce the side effects. Additionally, we find that the anti-CTLA-4 antibody should be administered following vaccination, and the dose of the antibody should positively correlate with the dose of vaccine within a safe range. Our study provides a theoretical basis for the selection of treatment regimens for clinical trials from a mathematical perspective.

Recently, immunogenic cell death (ICD) activated by phototherapy has attracted increasing attention in anticancer immunotherapy. Pyroptosis, a lysogenic and inflammatory form of cell death distinct from apoptosis, is considered to enhance the ICD process in tumor cells. Endoplasmic reticulum (ER)-targeted pyroptosis induced by phototherapy is reported to promote the release of inflammatory cytokines and DAMPs and amplify ICD response as a result. However, specific and stable tracking of the ER is more difficult than that of other organelles. In this work, we introduce a dual-modulation strategy to regulate the effect of ER-targeting unit p-toluenesulfonamide and twisting conjugation motif on the modification of heptamethine cyanine. A dimer dye (T780T-ER) with twisting structure and four p-toluenesulfonamide molecules is ultimately optimized, which can specifically target ER with good stability and efficient Type I PDT capability. Under PDT/PTT stimulation, T780T-ER activates sufficient pyroptosis and causes the release of inflammatory cytokines and DAMPs. In vivo, promoted ICD response and strengthened antitumor immunity are confirmed against the growth of primary and distant tumors. Summarily, this study highlights the importance of a multiple-modulation strategy in developing ER-targeted photosensitizers and proposes a Type I PDT molecule (T780T-ER) as an ER stress-dependent pyroptosis inducer to enhance antitumor immunotherapy.

Sustained increase in intraocular pressure (IOP) following intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in the treatment of retinal disease has been theoretically attributed to aggregation of anti-VEGF in the iridocorneal angle. However, previous studies by our group showed full clearance of intravitreally injected bevacizumab, aflibercept, and ranibizumab. The objective of this study was to further analyze and compare the clearance of these anti-VEGF agents from the eye after a single injection in a rat model.

Gastric cancer is a common malignant tumour. Copper-induced cell death, a recently discovered form of metal ion-related cell death, has garnered significant attention from researchers. We synthesised a multifunctional nanoparticle, ZnO@CuEA, and characterised its morphology using transmission electron microscopy. Cytotoxicity was analysed via CCK8 assays and calcein-AM staining. The tumour-targeting capability of ZnO@CuEA was validated using confocal microscopy and in vivo imaging experiments. RNA-seq and proteomic analysis were conducted to assess changes in mRNA and protein expression before and after ZnO@CuEA treatment. Lysosomal β-galactosidase staining was employed for cellular senescence detection, and protein expression levels were analysed via Western blot. Finally, in vivo experiments demonstrated the tumour-inhibitory effect of ZnO@CuEA. ZnO@CuEA is a multifunctional nanoparticle capable of targeting tumour cells and inducing cuproptosis. In vivo experiments showed that ZnO@CuEA exhibits significant antitumor activity. The multifunctional nanoparticles synthesised in this study provide a novel therapeutic approach for cancer treatment.

The patient presents with a genetic condition named Li-Fraumeni syndrome, which predisposes her to multiple neoplasms during her lifespan. Due to the chemotherapeutic treatment of an osteosarcoma, the patient presents with cardiotoxicity secondary to doxorubicin that is refractory to conventional management. The patient is initially stabilized with a peripheral veno-arterial extracorporeal membrane oxygenation device, with no improvement after 14 days of support. Later she was assisted with a HeartMate 3 mechanical circulatory device as a bridge to candidacy or as a destination therapy. She is the first paediatric patient in Spain to be assisted with long-term circulatory support using the HeartMate 3 device.

Doxorubicin is widely used in cancer treatment, and an effective drug carrier is usually needed to overcome its serious side effects. In this study, a highly monodisperse hollow covalent organic framework (HCOF) was prepared using a two-step method, and then was loaded with DOX with a high loading efficiency of 41.2 wt%. In vivo studies demonstrated excellent antitumor efficacy.

VCP/p97 plays an important role in endoplasmic reticulum related degradation pathways, and inhibition of p97 was shown to induce ER stress and subsequently cell death in a variety of solid tumors and hematoma. For acute myeloid leukemia (AML) cells, inhibition of p97 activity leads to the accumulation of ubiquitylated proteins, activation of unfolded protein response (UPR) and apoptosis.

High-dose methotrexate (HD-MTX) is seen as an effective therapy for acute lymphoblastic leukemia (ALL); however, it is extremely toxic. Monitoring the plasma concentrations of methotrexate (MTX) and its important metabolite, 7-hydroxy-methotrexate (7-OH-MTX), on a routine basis aids in dose modification of rescue medications and in avoiding toxicity. The pharmacologically active and toxic effects of drugs are due to the unbound portion, as most drugs are bound to plasma proteins to some degree. However, the simultaneous measurement of unbound plasma concentrations of MTX and 7-OH-MTX has not been reported.

Gynecological cancers represent one of the leading causes of death in women and pose a critical global health challenge. While surgery and chemotherapy remain the first-line therapies for gynecological cancers, the persistently high morbidity and mortality rates have driven the urgent exploration of novel theranostic strategies. In recent years, polymer nanoparticles (PNPs) have gained increasing attention in the diagnosis and treatment of cancer due to their superior targeting ability and delivery efficiency. This review provides an overview of PNPs and their role in tumor diagnosis and treatment, with a strategic focus on their utility in gynecological cancers. It covers drug delivery, imaging, combination therapy, and theranostic integration in gynecological cancers, and summarizes the composition, principles and characteristics of diverse polymers and their cargoes. Furthermore, this work highlights innovative applications of PNPs in gynecological cancers management, spanning chemotherapy, immunotherapy, PARPi therapy, phototherapy and other therapies. Despite promising preclinical advancements in PNPs, formidable challenges persist in their clinical translation. This review serves as a comprehensive resource for researchers and clinicians aiming to optimize gynecological cancers theranostics as well as accelerate the development and clinical translation of PNPs.

The hypoxic tumor microenvironment (TME) significantly impacts the effectiveness of various therapies on breast cancer. Conventional chemotherapeutic agents are unable to target hypoxic tumor tissue specifically, leading to reduced treatment efficacy and severe systemic toxicity. In order to improve drug targeting ability, we developed a bioactive biomotors system (MDPP@Bif) for chemoimmunotherapy against breast cancer. Utilizing the self-driving properties of the anaerobic Bifidobacterium infantis (B. infantis, Bif), both doxorubicin (DOX) and anti-programmed cell death protein ligand-1 (αPD-L1) antibody can be delivered simultaneously to tumor tissues to exert an anti-tumor effect on breast cancer.