Prostate cancer (PCa) is a prevalent malignancy in males with high morbidity and mortality. Although treatment modalities have evolved considerably, tumor resistance, recurrence, and metastasis persist, urgently requiring the exploration of alternative therapies for PCa. There is ongoing research on finding and identifying the use of traditional plant medicine (TPM). Cellular homeostasis comprises a sophisticated network of metabolic processes that functions cooperatively to preserve a stable intracellular environment. Programmed cell death (PCD) plays an important role in PCa mechanism. Thus, they represent an effective strategy for targeting PCa. TPM has been proven to induce PCD through multiple pathways and target in the treatment of PCa. Recent reviews have only focused on the one of the PCD, and autophagy, apoptosis, pyroptosis, ferroptosis, and necroptosis are not simultaneously reviewed.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of gastric cancer; however, they can lead to rare immune-related adverse events (irAEs) affecting the urinary system. Herein, we report a case of non-bacterial cystitis complicated by acute kidney injury (AKI) in a 59-year-old male patient with Alpha-fetoprotein-producing gastric carcinoma (AFP-GC). Following treatment with toripalimab combined with SOX chemotherapy, the patient developed urinary tract irritation symptoms, gross hematuria, and stage II AKI. Cystoscopy revealed diffuse mucosal hemorrhage, and biopsy demonstrated extensive infiltration of CD3+, CD8+, CD4+, and CD20+ lymphocytes, along with high PD-L1 expression and TIA-1 positivity, confirming the diagnosis of non-bacterial cystitis. A full-dose methylprednisolone pulse of 200 mg/day effectively alleviated the symptoms and restored renal function. This case underscores the importance of vigilance for urinary system irAEs in patients receiving ICIs, emphasizing that early identification and systematic evaluation are critical. Full-dose corticosteroids should be used for moderate to severe irAEs. Moreover, this report provides valuable insights into immunotherapy practice and toxicity management in the rare AFP-GC subtype.

The perioperative role of systemic therapy remains poorly defined in borderline resectable or unresectable non-head-and-neck locally advanced cutaneous squamous cell carcinoma (cSCC). We evaluated whether conversion-intent PD-1-based chemoimmunotherapy could restore surgical feasibility in this setting.

Ecteinascidins constitute a family of alkaloid compounds, originally isolated from marine tunicates, that exhibit strong antitumor activity. They act through binding to the DNA minor groove and forming covalent adducts with guanine residues. However, the limited availability of structural data restricts mechanistic insights into their mode of action and hampers the discovery of novel compounds. We report crystal structures of duplex DNA adducts with first-, second-, and third-generation ecteinascidins. The structures show that trabectedin, lurbinectedin, and PM54 bind through their shared A- and B-subunits, forming a covalent bond with the N2 atom of guanine and an extensive network of noncovalent interactions, leading to significant minor groove widening. In contrast, their C-subunit, which differs across the compounds, establishes distinct contacts with the modified strand that affect binding strength and sequence specificity. These structural findings, supported by Förster resonance energy transfer and biochemical assays, reveal the molecular determinants underlying differential sequence selectivity and reactivity. Our results provide a mechanistic framework for the anticancer activity of ecteinascidins and a structural basis to guide the design of next-generation analogues with improved therapeutic potential.

Three-dimensional (3D) cell culture systems provide superior simulation of the tumour microenvironment compared to traditional two-dimensional (2D) cultures. Chemoprevention agent curcumin analog-1.1 (CCA-1.1), a synthetic curcumin derivative, has demonstrated promising anticancer properties against triple-negative breast cancer (TNBC). This study aimed to develop and use a 3D agarose-based culture system for MDA-MB-231 cells to comprehensively evaluate the efficacy of CCA-1.1 as an anticancer agent.

Breast cancer stem cells (BCSCs) are responsible for chemotherapy resistance, metastasis, and tumor recurrence. Paclitaxel-primed mesenchymal stem cells (MSCs) can activate T cells, offering a novel immunotherapeutic approach. However, the molecular mechanisms underlying BCSC-immune interactions remain poorly understood.

Cancer continues to pose a significant worldwide health concern, underscoring the need for the identification of innovative, safer, and more effective therapeutic agents. Phytochemicals obtained from medicinal plants are progressively acknowledged for their anticancer efficacy. This work investigates the antimitotic and antiproliferative properties of the ethanolic extract of Benincasa hispida seeds (EeBHS), known as winter melon, from the Cucurbitaceae family.

Gastric cancer is a major global health concern characterized by high incidence and mortality rates. One of the key challenges in treating gastric cancer is the development of resistance to chemotherapy drugs like cisplatin (DDP). This study aimed to investigate the efficacy of Zuo Jin Wan (ZJW), a traditional Chinese medicine, in overcoming DDP resistance in gastric cancer cells.

With the improving survival rates of malignant tumors, the focus of attention in cancer research is shifting toward a better understanding of long-term treatment-related adverse effects that impact quality of life, with particular focus on cancer-related cognitive impairment. This phenomenon, commonly referred to as "chemobrain" in the literature, manifests as deficits in attention, memory, processing speed, and executive functions. Although the frequency of objectively measured cognitive deficits detected through neuropsychological assessments are moderate, subjective complaints often result in significant deterioration of quality of life. The present review aims to provide a multidisciplinary overview of chemobrain, emphasizing its epidemiological characteristics, neurobiological and psychosocial factors, and options for evidence-based psychological interventions. Alongside neurotoxic, inflammatory, hormonal, and neuroendocrine mechanisms associated with chemotherapy, the review highlights distress, cognitive compensation, and discrepancies between subjective complaints and objectively measurable cognitive deficits. Diagnostic challenges and evidence-based psychotherapeutic approaches-especially cognitive behavioral therapy (CBT), mindfulness-based interventions, and rehabilitation-are also discussed. This analysis highlights the complex nature of chemobrain and the need for further research to develop targeted, individualized therapeutic protocols.

Insulin resistance (IR) is involved in the development, progression, and treatment resistance of cancer. Apart from contributing to obesity and type 2 diabetes, IR leads to hyperinsulinemia, disruption of insulin-like growth factor signaling, chronic inflammation, and metabolic remodeling, which fosters a pro-tumorigenic milieu. These changes stimulate the PI3K-Akt-mTOR, MAPK, JAK-STAT, and NF-κB pathways, which increase proliferation, survival, angiogenesis, immune escape, and metastasis. IR also modifies the tumor microenvironment (TME) and dampens anti-tumor immunity. IGF-1R, IL-6, IL-1β, TNF-α, PD-1, PD-L1, and CTLA-4 monoclonal antibodies could be beneficial by inhibiting inflammatory and oncogenic pathways and reinitiating immune surveillance. Tumor resistance and heterogeneity are significant obstacles. This is a structured narrative review of the molecular connections, antibody treatments, translational obstacles, and future refined approaches in oncology.

The accelerated development of innovative anticancer therapies has led to the early approval of an increasing number of drugs. However, clinical evidence available at the time of approval is often limited, necessitating additional post-marketing studies to supplement safety and efficacy data. Therefore, post-marketing requirements (PMRs) have gained greater regulatory importance. Nevertheless, the current landscape of PMRs for anticancer drugs in Japan has not been clearly characterized. In this study, we aimed to characterize the status, content, and trends of PMRs for anticancer drugs approved in Japan. We reviewed publicly available regulatory documents for anticancer drugs approved in Japan between 2001 and 2024 and extracted data on background characteristics and PMRs. Analysis of 471 anticancer agents identified 328 (69.6%) drugs requiring at least one PMR. The temporal trend analysis showed a consistent increase in the number of drugs requiring PMRs after 2011. Among 453 PMR assignments, the development and implementation of a risk management plan (RMP) was the most frequent PMR type (n = 254, 56.1%), followed by post-marketing all-case surveillance (n = 147, 32.5%). Twelve drugs (2.6%) required post-marketing clinical trials, among which one (0.2%) involved dose optimization. In conclusion, our findings show that PMRs for anticancer drugs in Japan are predominantly focused on safety monitoring, and that only one PMR was related to dose optimization. These findings suggest that further consideration may be needed in Japan to strengthen post-approval evidence generation for dose setting and to support more evidence-based dose selection.

DNA double-strand breaks (DSBs) are the most severe DNA damage, and defective repair can lead to apoptosis or malignant transformation. DSBs are mainly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR), while microhomology-mediated end joining (MMEJ) serves as a backup pathway. Since DNA polymerase theta (Polθ) is essential for MMEJ, this pathway is also named Polθ-mediated end joining. Polθ is barely expressed in normal tissues but overexpressed in many cancers, making it a promising therapeutic target. In recent years, Polθ inhibitors and related therapeutic strategies have emerged rapidly, with clinical trials underway. This review summarizes the structure, function and expression of Polθ in tumorigenesis, highlights synthetic lethal strategies, drug development and clinical translation, and discusses current limitations and future directions for cancer research.

Fc-gamma receptors (FcγRs) regulate IgG antibody activity, and Fc-engineering is a proven method to improve the efficacy of tumor-targeting antibodies. Here, we explore tailored FcγR blockade to enhance the therapeutic efficacy and tolerability of immune checkpoint-blocking (ICB) antibodies.

The therapeutic efficacy for cervical cancer treatment is limited by insufficient drug accumulation and penetration due to physiological barriers such as mucin-rich environments after systemic administration. Thus, developing a local drug delivery system is essential to overcome these hindrances. Active transcytosis of cancer nanomedicines holds great promise for enhancing tumor extravasation, infiltration, and antitumor activity. Herein, polyzwitterionic OPDEA-PCL was developed to encapsulate paclitaxel (PTX) into micelles, serving as an intravaginal therapy for orthotopic cervical cancer. The OPDEA-PCL/PTX micelles efficiently penetrated mucus and exhibited strong resistance to mucin fouling, thereby facilitating rapid transcytosis into tumors. Furthermore, OPDEA-PCL/PTX micelles colocalized with the mitochondria of tumor cells, reversing PTX resistance. In the orthotopic cervical tumor model, the inhibition rate of OPDEA-PCL/PTX micelles was 90.0%, more than 2-fold higher than that of free PTX. In the subcutaneous cervical cancer model which is resistant to PTX. Intravenous administration of OPDEA-PCL/PTX micelles significantly overcame PTX resistance, achieving a tumor inhibition rate of 95.2%, and extending the median survival time by more than 2-fold compared to free PTX and PEG-PCL/PTX treated groups. In summary, this approach holds great promise as a potent localized nanomedicine for cervical cancer treatment with minimal side effects.

CD3-bispecific antibodies (CD3-BsAbs) represent an emerging modality with promising anticancer potential. Despite increasing regulatory approvals, the development of CD3-BsAbs remains challenging. CD3-BsAb candidates are routinely assessed and compared via in vitro workflows. However, protocol heterogeneity across experimental laboratories constrains cross-study potency comparisons. To address this, we developed an in vitro Quantitative System Pharmacology (QSP) model that mechanistically characterizes key processes underlying CD3-BsAb activity. The aim was to establish a framework adaptable to diverse in vitro conditions. The current framework comprises (a) single-cell trimer formation sub-model, (b) trimer-mediated T-cell activation and differentiation sub-model, (c) effector T-cell mediated tumor cell killing sub-model. We evaluated the framework using DuoBody-CD3x5T4 (CD3 equilibrium dissociation constant (KD) = 683 nM) data from 14 solid tumor cell lines spanning 5T4 expression of 9,447-61,686 molecules/cell and drug concentrations of 1.76E-05-42.8 nM. For a subset of cell lines, we also included additional data comparing DuoBody-CD3x5T4 with bsIgG1-CD3x5T4 (CD3 KD = 16 nM) and assessing effector-to-target (E:T) ratios of 1:1-8:1. All in vitro data were pooled into a single modeling dataset. A joint fit of T-cell activation and tumor cell cytotoxicity across the interconnected sub-models accurately captured the data and demonstrated mechanistic consistency. The model yielded mechanistically meaningful parameters, such as the per-T cell trimer count required to achieve half-maximal T-cell activation (EC50_act, estimated to be 2.12-4.6 trimers/T cell). The model's mechanistic structure and versatility suggest its potential to serve as a platform to predict drug effects across diverse assay conditions, quantify assay-dependent effects, and guide candidate selection.

Hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer is the most common type of advanced breast cancer. The addition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors to endocrine therapy (ET) has made a marked change to patient outcomes. While clinical trials have established their efficacy, real-world studies like this one are needed to confirm their effectiveness given the many variables which may arise in patient demographics and clinical presentation.

Immune checkpoint inhibitor (ICI)-induced cardiac immune-related adverse events (cardiac irAEs) are rare yet serious complications. Clinical assessment tools to identify at-risk patients would allow for more effective prevention strategies, thus improving clinical outcomes. We constructed various machine learning (ML) models to predict these events among patients receiving ICI therapy.

The primary objective of this study was to evaluate the efficacy of oral nutritional supplements (ONS) on chemotherapy tolerance and long-term survival outcomes in postoperative colorectal cancer patients undergoing chemotherapy.

Herein, some new carbohydrate-conjugated pyridine oximes were designed, synthesized, and evaluated as promising anticancer agents. The synthesized compounds were characterized using 1H NMR, 13C NMR, and HRMS spectroscopy. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines (MCF-7, MDA-MB-231, and A549) and a normal cell line (HEK-293) using the MTT assay. Among all the synthesized derivatives, compound 25 exhibited the most potent anticancer activity, with IC50 values of 4.26 ± 0.29 μM against MCF-7, 15.90 ± 0.95 μM against MDA-MB-231 and 8.36 ± 0.47 μM against A549 cells, compared to an IC50 value of 325.82 ± 3.05 μM against non-cancerous HEK-293 cells. The in silico molecular docking studies further supported its anticancer potential, showing strong binding affinities of -10.3 and -9.5 kcal/mol with EGFR and tubulin-combretastatin A4 protein respectively. Additionally, the ADME and toxicity predictions indicated favorable physicochemical characteristics, oral bioavailability, and drug-like profiles. The synthesized carbohydrate-conjugated pyridine oximes are found as a promising class of anticancer agents and highlight compound 25 as a potential lead for further preclinical studies.

Histone deacetylases (HDAC) overexpression is associated with oncogenesis. Hence, HDAC inhibitors are a promising class of compounds for targeted cancer therapy. Some HDAC inhibitors, such as vorinostat (SAHA), are already approved for the treatment of hematologic cancer. A number of 4-substituted anilides (para-aminophenol or para-aminobenzoic acid derivatives) were designed and synthesized as potential HDAC inhibitors. Compound 23e behaved as a potent HDAC2 inhibitor (IC50 = 4.2 nM) with greater activity than SAHA. Molecular docking results showed that the ligand 23e well placed to the HDAC2 active site through both hydrogen (Gly32, Asp104, Gly154, and His183) and hydrophobic (His33, Pro34, Phe155, His183, and Phe210) interactions. Molecular dynamics simulations confirmed stable complex formation over 500 ns with only small adaptive conformational fluctuations upon ligand binding. MM/PBSA analysis indicated a favorable binding free energy (ΔGbind = -27.98 kcal/mol), confirming a thermodynamically stable and dynamically compatible protein-ligand interaction. Compound 23e exhibited a pronounced antiproliferative effect comparable to SAHA against HeLa and Raji cells, with IC50 values of 5.07 ± 0.09 µM and 1.87 ± 0.22 µM, respectively, with low toxicity on normal cells. The synthesized derivatives can be considered as potential compounds for further development.