Phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the de novo Serine synthesis pathway (SSP), a highly regulated pathway overexpressed in several tumors. Specifically, PHGDH expression is dynamically regulated during different stages of tumor progression, promoting cancer aggressiveness. Previously, we demonstrated that high Serine (Ser) availability, obtained by increased exogenous uptake or increased PHGDH expression, supports 5-Fluorouracil (5-FU) resistance in colorectal cancer (CRC). Beyond its metabolic role in sustaining Ser biosynthesis, different "non-enzymatic roles" for PHGDH have recently been identified. The present study aims to investigate non-enzymatic mechanisms through which PHGDH regulates 5-FU response in CRC.

Unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombosis (PVTT) has poor prognoses. This study evaluated the efficacy and safety of lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) and locoregional therapy (LRT) in uHCC patients with PVTT.

The increasing global incidence of cancer emphasizes the vital role of machine learning algorithms and artificial intelligence (AI) in identifying novel anticancer targets and developing new drugs. Computational approaches can significantly quicken research on complex disorders, enabling the discovery of effective treatments. This study explores anticancer targets by assessing the potential of naturally occurring compounds derived from various plants to cure colorectal cancer. Twenty compounds were sourced from PubChem, and the RPS20 protein structure was obtained from AlphaFold, and mutation "V50S" was added. Validation of mutated RPS20 protein was performed using the Ramachandran plot and ERRAT. Binding sites on the mutated RPS20 protein were identified with DeepSite, followed by virtual screening to pinpoint the most promising natural lead drug candidate. Indirubin emerged as the lead drug candidate, fulfilling all ADMET criteria and exhibiting a good binding affinity. Further development included designing an AI-based drug using the WADDAICA server, which was validated through molecular docking, molecular dynamics (MD) simulation, and MMGBSA. The electronic properties of indirubin were studied using DFT calculations. The results show a moderate HOMO-LUMO gap, indicating its potential reactivity and the possible capability for biological target interactions. These findings indicate that indirubin could serve as a potent and effective cancer inhibitor, offering high efficacy with minimal side effects.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, significantly improving outcomes for various malignancies. Despite their clinical success, only a subset of patients benefits from ICIs treatment, underscoring the need for innovative strategies to enhance their therapeutic potential. Ferroptosis, a unique form of programmed cell death driven by iron-dependent lipid peroxidation, has emerged as a promising partner for enhanced immunotherapy. Combining ferroptosis inducers with immune checkpoint blockade has shown promising potential in improving the efficacy of cancer immunotherapy. This study explores the mechanisms of ferroptosis and immune checkpoint inhibitors for synergistic cancer treatment, and reviews recent delivery platforms integrating ferroptosis and immune checkpoint blockade for enhanced therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers like malignant melanoma. However, they can lead to a range of immune-related adverse events (irAEs), impacting various organ systems. Among these, myositis is a rare but serious irAE, typically characterized by myalgia, muscle weakness, and elevated creatine kinase (CK) levels. Herein, we report the case of a 58-year-old female with advanced melanoma, who presented a delayed-onset of ICI-induced myositis accompanied by severe muscle weakness. Interestingly, the CK levels remained normal throughout her disease course. Neurological examination, MRI, and electromyography were pivotal in diagnosing myositis. Differential diagnoses, including myasthenia gravis, myocarditis, and paraneoplastic syndromes or idiopathic inflammatory myopathies, were systematically ruled out through clinical evaluation, serological testing, and imaging. The patient responded favorably to high-dose corticosteroid therapy, leading to a gradual improvement of symptoms and no relapse after stopping treatment. This case report emphasizes a multimodal diagnostic approach and underscores the importance of clinical awareness for such atypical irAE presentations.

Immune checkpoint inhibitor (ICI) has reshaped the treatment landscape of esophageal squamous cell carcinoma (ESCC). But most patients end up with disease progression and/or therapeutic intolerance. The subsequent ICI rechallenge raises some discussions.

Currently, given variations in the abnormal tumor microenvironment (TME), significant progress has been made in the treatment of breast cancer (BC) based on TME-responsive nanosystems-mediated ferroptosis. Due to inherent deficiencies such as the limited efficacy of Fe-induced catalysis, the lack of endogenous hydrogen peroxide (H2O2), and the overexpression of glutathione (GSH) in tumor cells, the treatment of ferroptosis is restricted. Here, this document highlighted polymeric nanoparticles with GSH resection (ssP-tHB@Fe/DOX), demonstrating significant improvements in TME responses, biocompatibility, and anti-tumor effects. Our study offers a platform for combined BC amplification therapy involving ferroptosis and DOX-induced chemotherapy, and it highlights the use of 3,4,5-trihydroxybenzaldehyde (tHB) in a Fe(III)-Fe(II) cyclic reaction to deplete GSH and enhance ferroptosis. Notably, ssP-tHB@Fe/DOX could effectively disrupt mitochondrial structure and reduce membrane potential in tumor cells, leading to decreased ATP production, depletion of GSH via multi-channel approach, inhibition of GPX4 expression, and accumulation of lipid peroxidation, thereby inducing ferroptosis enhancement to achieve BC therapy. Meanwhile, the release of the anticancer drug DOX has dual effects: it interferes with NADPH to enhance the Fe-mediated Fenton reaction and induces apoptosis in tumor cells. Moreover, RNA sequencing (RNA-seq) analysis robustly supported the anti-tumor mechanism of ssP-tHB@Fe/DOX, confirming involvement in the amino acid metabolism ferroptosis signaling pathway and the p53 signaling pathway, etc. Therefore, in this study, we thoroughly introduced the design of intelligent nanosystems, proposed methods to enhance DOX-induced apoptosis and ferroptosis, offering a novel approach for cancer treatment.

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disease characterized with mutiple organ tumors. Tyrosine kinase inhibitor (TKI) is one of the targetd treatment for VHL syndrome. Lenvatinib (LEN), an oral small-molecule multiple TKI, and proteinuria is one of the most common adverse events associated with LEN. We reported a case of lenvatinib-induced nephrotic syndrome in a Chinese patient with VHL syndrome. The renal biopsy was proved with thrombotic microangiopathy (TMA) and focal segmental glomerulosclerosis (FSGS)-like pattern. Drug-induced kidney injury deserves further attention.

OM is a very relevant and sometimes therapy-limiting side effect of CT/RCT. There are prophylactic and therapeutic measures available that should be recommended to all patients. This study investigated how patients were informed about oral mucositis (OM) as possible side effect of CT/RCT, how well they knew about available prophylactic and therapeutic measures from the clinical guidelines and to what extent they applied these.

The plant kingdom is a crucial source of potential medicines, with medicinal plants playing a significant role, they have been used to treat various diseases, including cancer. Phytochemicals have emerged as promising candidates for enhancing conventional cancer treatment strategies, particularly in addressing the persistent challenges associated with such therapies. For a long time, combined therapy has been widely adopted to overcome the limitations of monotherapies. To optimize therapeutic outcomes, it is crucial to understand the mechanisms underlying the interactions between phytochemicals and conventional drugs. Based on the above, we have developed a database named InterPAD, which serves as a valuable resource to retrieve detailed information on the interactions between phytochemicals and anticancer drugs. It offers insights into their mechanisms of action and therapeutic effects, thereby facilitating a deeper understanding of how these phytochemicals can be effectively integrated into modern cancer treatment protocols. A total of 1,055 interactions involving 331 phytochemicals and 244 anticancer drugs were meticulously reviewed and manually curated from the original publications into the InterPAD database. Additionally, InterPAD curates from 680 medicinal plants, providing detailed phytochemicals-related plant information. The database also includes 619 regulatory molecules and 74 cancer types, sourced from other databases, to elucidate cancer-specific molecular mechanism and therapeutic effects. To our knowledge, InterPAD is the first comprehensive database to investigate the synergistic or antagonistic interactions of phytochemicals with drugs across various cancer types. It uniquely highlights the biological effects of phytochemicals-based anticancer interactions through the framework of "multiple-regulatory molecules and multiple-signaling pathways", providing insights into their molecular mechanisms. This resource serves as a valuable tool for advancing research and improving cancer treatment strategies. InterPAD is accessible at: https://bddg.hznu.edu.cn/interpad/ .

Prostate cancer (PCa), a common urinary malignancy, is the leading cause of mortality and morbidity among men worldwide. Curcuma amada extract has demonstrated antitumor properties in preclinical models of various cancers, however, its mechanisms against prostate cancer remain unclear. The current study aims to investigate the underlying mechanism of C. amada rhizome extract (CARE) in treating PCa through network pharmacology, bioinformatics analysis and in-vitro experiments. UHPLC-QTOF-HRMS/MS detected 16 phytoconstituents in C. amada, with 15 constituents passing drug-likeness criteria. Public databases identified 1,311 CARE and 473 PCa related targets, with 59 overlapping targets. PPI analysis revealed P53, CTNNB1, EGFR, AKT1, ESR1, HIF1A, CCND1, PIK3CA, and BCL2 as hub targets. Further,4-hydroxycinnamic acid, 13-hydroxylabda-8(17),14-dien-18-oic acid, labda-8(17),12-diene-15,16-dial, zederone, zedoarondiol, zerumin A and caffeic acid were identified as core compounds with high degree values. GO and KEGG analysis identified targets primarily associated with apoptosis and PI3K-AKT signalling pathway. Molecular docking confirmed good binding potential of core compounds with key hub targets, while molecular dynamics (MD) simulation validated the stability of these interactions with minimal fluctuations throughout the simulation. Additionally, mRNA expression levels, immune infiltration and genetic alteration of the hub targets were analyzed. CARE significantly inhibited the proliferation of PC-3 cells, induced apoptosis, and caused G2/M phase arrest. In addition, qRT-PCR analysis revealed that CARE was able to suppress mRNA expression of genes involved in the PI3K-AKT signalling pathway. Thus, the study highlights the underlying mechanism of CARE as a promising treatment option for prostate cancer.

Nanocrystals have great potential as improved drug carriers due to their low cost, high biodegradability, and biocompatibility. Thus, cellulose nanocrystals (CNCs) are particularly suitable for enhanced antibacterial and anticancer therapy. In this research, we report the green synthesis of β-cyclodextrin-functionalized cellulose nanocrystals (β-CD/CNCs) from pistachio shells as a carrier material for propolis, as well as the determination of its antibacterial and anticancer properties. The β-CD/CNCs were characterized using Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). FTIR analyses indicated the successful attachment of β-cyclodextrin to the cellulose nanocrystals. FE-SEM and TEM images of β-CD/CNCs exhibited rod-shaped morphology, while the XRD pattern revealed the crystal structure of β-CD/CNCs. The chemical composition of the propolis extract was investigated using GC-MS analysis. The incorporation of the propolis extract into the β-CD/CNCs was achieved with 10% encapsulation using the differential weighing method. Subsequently, the antibacterial and anticancer properties of the propolis-loaded β-CD/CNCs were determined. The antibacterial activity was assessed using the disk diffusion method (Kirby-Bauer method) and minimum inhibitory concentration (MIC) determination by the dilution method (DM). The anticancer properties were evaluated using MTT and flow cytometry assays on two liver cell lines (HepG2 and L929). The results demonstrated that the propolis loaded in β-CD/CNCs exhibited better antibacterial and anticancer activity than free propolis. Therefore, β-CD/CNCs can be suggested as a suitable carrier for propolis.

The use of immune checkpoint inhibitors (ICIs) is increasingly important in melanoma management. While ICIs are associated with immune-related adverse events (irAEs), little is known about skeleton irAEs and they are felt to be poorly described.

Immune checkpoint inhibitors targeting negative regulatory checkpoints including programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 have produced significant improvements in progression-free survival (PFS) and overall survival in multiple solid tumors. Lymphocyte activation gene 3 (LAG-3) is an inhibitory receptor that is highly expressed by exhausted T cells. Dual blockade of LAG-3 and PD-1 with monoclonal antibodies relatlimab and nivolumab has improved PFS in advanced melanoma, leading to Food and Drug Administration approval for this indication. Concurrently, enthusiasm for targeting LAG-3 has been tempered by negative results in multiple indications, although novel approaches including LAG-3-directed bispecifics tebotelimab continue to demonstrate promise. In this review, we discuss the current understanding of LAG-3 in regulating antitumor immunity and the ongoing state of clinical development of LAG-3-directed agents in cancer.

To identify predictive gene-expression signatures for immune-related adverse events (irAEs) in patients with melanoma treated with anti-PD-1 inhibitors, in the adjuvant therapy (AT) and first-line therapy (FLT).

Dried Embelia ribes berries can be used to extract Embelin (2,5-Dihydroxy-3-undecylcyclohexa-2,5-diene -1,4-dione), a herbal p-benzoquinone derived from general quinones. This plant shows potential for scientific study that could provide cutting-edge therapeutic compounds. Prior studies have shown that the molecule's transformation into a complex may have increased its bioactivity. Furthermore, it has been shown that inorganic complexes are more versatile than pure organic molecules, which may improve the ability to target sites that are commonly present in the aquatic ecological environment.

Angiogenesis is critical in intrahepatic cholangiocarcinoma (ICC), a highly lethal cancer with limited treatment options. Sunitinib, a multi-receptor tyrosine kinase inhibitor, has strong antiangiogenic and antitumor effects. We aimed to evaluate the efficacy and tolerability of sunitinib as a second-line treatment in chemotherapy-pretreated patients with advanced ICC.

Pancreatic cancer (PC) is currently a leading cause of death worldwide and its incidence is expected to increase in the following years. Chemotherapy with gemcitabine (GEM) is precluded by extensive enzymatic inactivation and clearance, and the nonspecific tissue distribution contributes to unwanted systemic toxicity and tumor resistance. In this work, GEM was encapsulated in d-ɑ-tocopheryl polyethylene glycol succinate (TPGS) micelles by 'stapling' GEM at 4-NH2 position with vitamin E succinate (VES) through a highly stable amide bond, achieving successful GEM hydrophobization by means of a prodrug system (VES-GEM). Recurring to solvent evaporation methodology, TPGS/VES-GEM (6/1 molar ratio) micelles were prepared, optimized regarding TPGS-to-VES-GEM ratio, and characterized regarding size, surface charge, polydispersity index, morphology, drug loading, and encapsulation efficiency (EE). Furthermore, purification methods were explored together with VES-GEM release profile and stability. Lastly, cell viability and cellular uptake of the formulation were analyzed in 2D and 3D BxPC3 cell line models. TPGS/VES-GEM micelles (6/1) showed ultra-small size (∼30 nm), and remarkable EE (>95%) together with ability to retain VES-GEM for long period of time (>7 days) with high stability. The micelles demonstrated exceptional cell cytotoxic activity for concentrations of 10 and 100 µM VES-GEM (∼0% cell viability) which may be explained by concerted action of GEM, VES, and TPGS. The nanocarrier was further enriched with PC cell membrane nanovesicles, displaying size ∼150 nm, ZP ∼ -30 mV and PDI ∼0.2 to improve biointerfacing properties and targeting properties. BxPC3 cell membrane-modified TPGS/VES-GEM micelles may be attractive biomimetic nanosystem for next-generation PC therapeutics.

Intravitreal anti-vascular-endothelial growth factor (anti-VEGF) injections have revolutionized the treatment of diabetic macular oedema (DME). The effect of early initiation of anti-VEGF treatment with good baseline visual acuity on treatment outcomes was compared with that of deferred treatment in patients with type 1 diabetes (T1D) and DME.

Bladder cancer (BLCA) remains heavily dependent on bacillus Calmette-Guérin (BCG) therapy due to the profound heterogeneity of its tumor microenvironment (TME) and deregulated metabolic landscapes. Taurine metabolism (TM) is a pivotal axis in BLCA, exhibiting dual roles in tumor progression and immune evasion. Deciphering the molecular mechanisms by which TM reprogramming fosters immunosuppression is imperative for advancing BLCA immunotherapy.