sirolimus

We integrate data on epidermal growth factor receptor inhibitors, phosphoinositide-3-kinase inhibitors, taxanes such as docetaxel, fluoropyrimidines such as capecitabine, immune checkpoint inhibitors, BRAF and MEK inhibitors, mechanistic target of rapamycin inhibitors, Bruton tyrosine kinase inhibitors and chimeric antigen receptor T-cell therapy. We highlight the vulnerability of older adults, in whom age-related skin changes, comorbidities and polypharmacy amplify the impact of these events while evidence from dedicated prospective studies remains scarce. The review synthesizes practical, mechanism-oriented strategies for prevention and stepwise management, from basic skin care and photoprotection to targeted use of antibiotics, corticosteroids and treatment modification, with the goal of supporting timely recognition of cutaneous toxicity and multidisciplinary care that preserves both quality of life and the anticancer efficacy of therapy.

This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.

P2, N=57, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed

Intrinsic S701 underwent reversible phosphorylation catalyzed by mechanistic target of rapamycin complex 1 (mTORC1) and protein phosphatase 2A (PP2A)...Pharmacological inhibition of PP2A sustained p-S701 and alleviated colon inflammation in wild-type but not in ΔS701 mice. Our findings highlight the importance of STAT3 heterogeneity in colonic inflammation and colorectal cancer.

P1/2, N=50, Active, not recruiting, University of Chicago | Trial completion date: Oct 2025 --> Oct 2030 | Trial primary completion date: Oct 2025 --> Oct 2030

P2, N=10, Recruiting, University of Chicago | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

A key finding from drug sensitivity analysis was that the high-risk group exhibited significantly increased sensitivity to several drugs, including CCT018159, rapamycin, vinblastine, metformin, and roscovitine. Moreover, the expression levels of SESN3, CRIP1, DPP4 and PIK3CA were significantly upregulated in breast cancer samples compared to control samples. This study constructed a risk model based on seven prognostic genes, offering new potential strategies for breast cancer therapy.

At the pathway level, PTM programs interface with Wnt/β-catenin and bone morphogenetic protein/SMAD axis and integrate mitogen-activated protein kinase (p38/c-Jun N-terminal kinase) → runt-related transcription factor 2 in regeneration, whereas in OSCC/cancer stem cell they converge on Janus kinase/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin, and transforming growth factor-beta/SMAD-driven epithelial-mesenchymal transition. This review expounds on recent advances in PTM-mediated regulatory mechanisms in dental-derived mesenchymal stem cells, outlines their functional implications in inflammatory and tumor microenvironments, and discusses translational strategies-including localized, time-staged PTM modulation for regeneration and pathway-anchored combinations for OSCC-for regenerative medicine and targeted cancer therapies. Future research directions emphasize the integration of single-cell and spatial multi-omics with PTM profiling as a new approach to precision-based dental and oncological therapies.

Activation of autophagy by rapamycin counteracted the effects of EIF2AK3 knockdown on both autophagy and PI3K/AKT signaling. Consistently, EIF2AK3 silencing in xenograft models enhanced the therapeutic efficacy of DDP by suppressing autophagy and attenuating PI3K/AKT activation. Collectively, our findings indicate that EIF2AK3 is a critical regulator of hypoxia-triggered autophagy in NSCLC, and targeting EIF2AK3-mediated PI3K/AKT signaling may represent a promising strategy to overcome cisplatin resistance.

P1, N=17, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

Notably, USP5 stabilizes C2CD5 through deubiquitination, thereby activating the phosphoinositide 3-kinase (PI3K)/ (protein kinase B) AKT/ mechanistic target of rapamycin (mTOR) signaling pathway and enhancing glycolytic flux via the HIF-1α transcription factor to drive AML progression. Importantly, USP5 knockdown enhanced the chemosensitivity of AML cells, and its small-molecule inhibitor potently curbed AML cell growth and proliferation. Generally, our findings establish the USP5-C2CD5 as a novel therapeutic target for AML treatment.

By conjugating the BCR-ABL inhibitor dasatinib with the LC3B-binding ligand GW5074, we engineered eight distinct ATTEC variants with diverse linkers...The activity of DS-PPE-GW was further enhanced by the autophagy activator rapamycin, confirming its autophagy dependence. Notably, DS-PPE-GW did not increase global autophagic flux, suggesting selective engagement of pre-existing autophagosomes. These findings demonstrate that strategically designed ATTECs can efficiently degrade BCR-ABL, targeting both its catalytic and non-catalytic functions, and provide a promising strategy for next-generation CML therapy.