In parallel, suppression of anabolic signaling, particularly impairment of the insulin-like growth factor-1/Akt/mechanistic target of rapamycin complex 1 (mTORC1) pathway, has been reported, indicating a shift in muscle protein turnover toward a catabolic state. By distinguishing drug-induced muscle toxicity from cancer cachexia and other wasting conditions, we propose that skeletal muscle should be recognized as a clinically relevant but underestimated target organ of cisplatin toxicity. Improved understanding of these processes may support the development of strategies to preserve muscle mass and function during cancer chemotherapy.

In addition, SGO2 compromised the cisplatin (CDDP) sensitivity of LUAD in vitro and in vivo...Silencing SGO2 with OA improved LUAD chemo sensitivity. Our work highlights the potential of SGO2 as a target for therapeutic intervention and OA as a food-bioactive compound for LUAD treatment.

Adjuvant ADC+ICI showed comparable short-term OS and directionally favorable DFS/PFS trends versus GC, with a distinct toxicity profile. These findings are hypothesis-generating and require prospective validation.

Compared to temozolomide (TMZ), PLB more potently inhibited the viability of PDFS cells...The mechanism involves suppression of the Nrf2/FTH1 pathway, subsequent upregulation of NCOA4, and ferritinophagy-driven iron overload. These results identify PLB as a potential ferroptosis inducer and warrant further investigation into its therapeutic potential for NFPA.

P1, N=48, Recruiting, Sawa Ito, MD | Not yet recruiting --> Recruiting

P1/2, N=18, Completed, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Active, not recruiting --> Completed

Proteomics analysis revealed a strategic mechanism to resist TMZ-induced apoptosis by upregulating exosomal proteins associated with biogenesis, chemoresistance, and therapeutic adaption. This finding revealed a considerable TMZ resistance mechanism and provided a new inspiration for preventing exosome biogenesis to resensitise TMZ cytotoxicity towards GBM.

Drug testing with temozolomide (TMZ) demonstrated reduced sensitivity under hypoxic conditions, shown by a 56% increase in IC50, reflecting clinically relevant therapy resistance. These findings show the ability of the model to mimic key properties of the GBM microenvironment at both phenotypic and molecular levels and offer a physiologically relevant platform to study GBM biology and evaluate therapeutic responses.

Anticancer activity of the racemic complexes C1-C4 against human colorectal adenocarcinoma (HT-29) and human lung cancer (A549) cell lines assessed using MTT assay indicated the IC50 concentrations ranging from 15.39 to 21.86 µM and 17.29 to 24.29 µM for HT-29 and A549 cells, respectively, and the values are comparable to that of the positive control (cisplatin) and also the same assay was performed on human epithelial kidney cells (HEK-293) to determine the selectivity index of the complexes...The complexes demonstrated favorable binding interactions with B-DNA, BSA, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2), with high binding affinity values of -8.12, -6.6, -6.25 and -7.53 kcal mol-1, respectively. Simultaneously, binding interactions of the individual enantiomers (R and S) of the respective pairs of each complex towards the target proteins were also examined, but they did not vary greatly among the complexes.

PRONano is brain-targeted, rationally designed nanoformulation which can overcome major A1874 delivery constraints. This strategy augmented PROTAC delivery and therapeutic potential in GBM, supporting future preclinical development.

GALNT5 facilitates malignant progression in CRC by promoting O-GalNAc glycosylation of EGFR and thereby activating the PI3K/Akt pathway, and confers resistance to L-OHP and 5FU through upregulation of ABCC1. These findings suggest GALNT5 as a potential diagnostic biomarker and a promising therapeutic target for overcoming chemoresistance in CRC.

P2, N=64, Recruiting, Virginia Commonwealth University | Trial completion date: Jan 2033 --> Jan 2032 | Trial primary completion date: Jan 2028 --> Jan 2030