sirolimus / Generic mfg. - LARVOL DELTA

Click Chemistry-Assisted Rejuvenation of Aging T Cells Sensitizes Aged Mice to Tumor Immunotherapy. (PubMed, J Am Chem Soc) - "Our study aims to rejuvenate aging T cells within tumor-draining lymph nodes (TdLNs) by using targeted delivery of rapamycin, a macrolide capable of mitigating aging-related decline in immune function, thereby enhancing the antitumor efficacy of immunotherapy in aged mice...Experimental data demonstrate that this approach has effectively restored the functionality of impaired CD8+ T cells in aged mice, thereby enhancing the antitumor response to immune checkpoint blockade (ICB) therapy to levels comparable to those in young mice. This study presents a promising strategy to combat the resistance to immunotherapeutic approaches commonly encountered among elderly tumor patients."

Journal • Preclinical • Oncology

Lymphatic malformations in childhood and adolescence (PubMed, Radiologie (Heidelb)) - "Patients with LM should be referred to an expert center to enable an early diagnosis and treatment in an interdisciplinary team. Together with the clinical and genetic findings MRI and MR lymphangiography enable the evaluation of interventional and surgical treatment options."

Journal • Review • Inflammation

Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies (clinicaltrials.gov) - P1/2 | N=89 | Completed | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ May 2024 | Trial primary completion date: Sep 2025 ➔ May 2024

Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Juvenile Myelomonocytic Leukemia • Multiple Myeloma • Natural Killer/T-cell Lymphoma • Oncology • Primary Central Nervous System Lymphoma • FLT3 • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1 • KMT2A

Specific drugs for rare diseases in a province of eastern China under catalog management: from 2021 to 2023. (PubMed, Front Pharmacol) - "Spesolimab, Sodium Phenylbutyrate, Nitisinone and Emapalumab are currently in short supply, and the delivery rate of 16 drugs such as Selumetinib, Sirolimus (tablet), Octreotide, Dimethyl Fumarate and Lanreotide is below 80%...This indicates a generally high level of accessibility to drugs for rare diseases in China. However, attention should be given to improving the supply capacity for drugs that are in short supply and have a low delivery rate."

Journal • Rare Diseases

Recent Advances and Challenges in the Treatment of Advanced Pancreatic Cancer: An Update on Completed and Ongoing Clinical Trials. (PubMed, Cancers (Basel)) - "This includes adagrasib (a KRAS inhibitor), olaparib (a PARP inhibitor for BRCA mutations), APG-1387 (an IAP antagonist), minnelide (an anti-stromal agent), arimastat (an MMP inhibitor), MK-0646 (an IGF1R inhibitor), sirolimus (an mTOR inhibitor), and metabolic inhibitors. Furthermore, we have summarized novel approaches such as cancer vaccines and ablation techniques as emerging strategies in the treatment of advanced pancreatic cancer. We have also examined the challenges in treating advanced pancreatic cancer and the factors contributing to therapeutic failure, which may offer valuable insights for developing more effective treatment strategies and innovative drug designs."

Journal • Review • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRCA • KRAS

Stress-induced sympathetic stimulation inhibits sorafenib-induced ferroptosis in renal cell carcinoma (AACR 2025) - "Isoproterenol (ISO), a non-specific β-adrenergic receptor agonist, was added into RCC cell lines ACHN and A498 before the addition of clinically-used-drugs (sorafenib, cabozantinib, lenvatinib, and rapamycin), and cell viability was analyzed by MTS assay... Stress-induced sympathetic stimulation inhibits sorafenib-induced ferroptosis in RCC."

Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ADRB2

Novel Therapies for Neurofibromatosis Type 1-Associated Inoperable Plexiform Neurofibromas: A Systematic Literature Review (ISPOR 2025) - "These reported on a total of 21 unique studies on 11 emerging therapies: 6 MEK inhibitors (selumetinib, mirdametinib, trametinib, binimetinib, FCN-159, tunlametinib) and 5 targeted anti-cancer agents (cabozantinib, tipifarnib, sorafenib, sirolimus, everolimus)... The promising results of MEK inhibitors in therapeutic trials for NF1 demonstrate that targeting the MAPK/ERK pathway is an attractive therapeutic avenue for unresectable PNs. Because selumetinib is only approved for children, future reimbursement will require advanced studies establishing MEK inhibitor efficacy in adults."

Review • Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • NF1

Study on the mechanism of action of Penehyclidine hydrochloride on LPS-induced acute lung injury by regulating autophagy through the mTOR/Keap1/Nrf2 signaling pathway. (PubMed, J Pharm Biomed Anal) - "To confirm the role of autophagy in the protective effects of PHC against ALI, we administered PHC in combination with Rapamycin (RAPA) or 3-Methyladenine (3-MA) to the model groups and evaluated the aforementioned parameters...Treatment with the mTOR inhibitor (autophagy inducer RAPA) blocked the protective effects of PHC on lung injury, the mTOR/Keap1/Nrf2 signaling pathway, and autophagy, while co-treatment with the autophagy inhibitor 3-MA showed a significant protective effect on ALI. The results suggest that PHC has a notable protective effect on ALI, which may be achieved by modulating the mTOR/Keap1/Nrf2 signaling pathway to inhibit autophagy."

Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • BECN1 • IL18 • IL1B • MPO • TNFA

mTOR controls ependymal cell differentiation by targeting the alternative cell cycle and centrosomal proteins. (PubMed, EMBO Rep) - "We demonstrate that mTORC1 inhibition by rapamycin preserves the progenitor pool by reinforcing quiescence and preventing alternative cell cycle progression for centriole amplification...By phosphoproteomic and phosphomutant analysis, we reveal that the mTORC1-mediated phosphorylation of GAS2L1, a centrosomal protein that links actin and microtubule cytoskeletons, participates in centriole disengagement. This multilayered and sequential control of ependymal development by mTORC1, from the progenitor pool to centriolar function, has implications for pathophysiological conditions like aging and hydrocephalus-prone genetic diseases."

Journal • CNS Disorders • Genetic Disorders • Ventriculomegaly

Pulmonary vein stenosis: future optimism. (PubMed, Curr Opin Cardiol) - "An aggressive approach of frequent reinterventions is a necessary strategy rather than treatment failure. More granular understanding of the mechanisms underlying PVS leading to novel muti-pronged anatomic and suppressive therapy are yielding improved survival.Multispecialty PVS teams at the institutional level and multiinstitutional collaboration, now possible via the PVS registry, are crucial to optimal care and future progress."

Journal • Pediatrics • Rare Diseases

GRIA1 Alleviates Sevoflurane-Induced Neurotoxicity by Suppressing Autophagy. (PubMed, J Biochem Mol Toxicol) - "The neurotoxicity caused by inhaled anesthetics has attracted more attention. Furthermore, the autophagy inducer rapamycin reversed GRIA1 overexpression-mediated promotion of cell viability and suppression of cell apoptosis and autophagy of HT22 cells upon SEV induction. GRIA1 improved SEV-induced neurotoxicity by suppressing autophagy."

Journal • Anesthesia • GRIA1

Phase 3 Trial of eRapa in Patients With Familial Adenomatous Polyposis (clinicaltrials.gov) - P3 | N=168 | Not yet recruiting | Sponsor: Rapamycin Holdings Inc.

New P3 trial • Genetic Disorders

LPM electrode loaded with RAPA-PLGA drug sustained-release system can reduce local fibrous tissue hyperplasia and local bioelectrical impedance. (PubMed, Eur J Med Res) - "The LPM electrode loaded with RAPA-PLGA demonstrates significant, sustained drug release and anti-proliferative effects in vitro. This drug-loaded electrode has been deemed safe for implantation in animal models. It can effectively inhibit local fibrous tissue proliferation and reduce local bioelectrical impedance, offering a technical strategy to prolong the in vivo functionality of LPMs and enhance clinical procedures."

Journal

Mechanism of lncRNA gadd7 regulating mitofusin 1 expression by recruiting LSD1 to down-regulate H3K9me3 level, and mediating mitophagy in alveolar type II epithelial cell apoptosis in hyperoxia-induced acute lung injury. (PubMed, Cell Biol Toxicol) - "LncRNA gadd7 regulated MFN1 expression by recruiting LSD1 to down-regulate H3K9me3 level and mediate mitophagy, thereby promoting AEC II apoptosis in HALI."

IO biomarker • Journal • Acute Lung Injury • B Cell Lymphoma • Lymphoma • Oncology • Respiratory Diseases • BCL2 • CASP3 • IL1B • IL6 • MFN1 • TNFA

A ZIF-8-based dual-modal smart responsive nanoplatform for overcoming radiotherapy resistance in advanced tumors. (PubMed, Nanoscale) - "In this study, we utilized ZIF-8, a type of metal-organic framework, to simultaneously load ICG and rapamycin for X-ray sensitization and combined photothermal therapy...It releases drugs in the specific tumor microenvironment, enhancing photothermal and radiotherapy sensitization effects. The results show that the smart dual-loaded nanoplatform effectively combines photothermal therapy and external-beam sensitization, reshapes the immunosuppressive tumor microenvironment and significantly inhibits tumor proliferation in the HepG2 subcutaneous xenograft model, demonstrating marked antitumor activity and good biosafety."

Journal • Oncology

Rapamycin alters the feeding preference for amino acids and sugar in female Drosophila. (PubMed, J Gerontol A Biol Sci Med Sci) - "However, such changes in macronutrient preferences were absent in males and sterile mutant females. Collectively, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, and this effect is influenced by both sex and reproductive status."

Journal

Impaired Drug Metabolism Caused by Compound Heterozygous Loss-of-Function Variants in CYP3A4: A Case Report. (PubMed, Clin Pharmacol Ther) - "We here describe the clinical presentation of a child with an extremely high sirolimus blood concentration (88.4 μg/L; therapeutic range at trough: 5-15 μg/L) and prolonged elimination half-life of 121 hours (mean 14 hours in the pediatric population) following only eight standard-dose administrations...This revealed that the patient is compound heterozygous for two rare loss-of-function variants in CYP3A4 (*8/*20). This clinical case highlights that a routine pharmacogenetic test panel that includes *22 as the only CYP3A4 variant is not a suitable diagnostic test for individuals with an increased pre-test probability of altered CYP3A4 metabolism."

Journal • Pediatrics • CYP3A4

Pharmacokinetics and tissue distribution of intranasal administration of rapamycin in rats. (PubMed, Xenobiotica) - "We also discovered gender differences in drug absorption following intranasal administration of rapamycin, wherein rapamycin exhibited faster systemic absorption in female rats compared to males. Our study demonstrated that intranasal administration of rapamycin is highly effective and low toxic, which may provide a new delivery option for rapamycin therapy in brain diseases."

Journal • PK/PD data • Preclinical • CNS Disorders • Epilepsy

Mycobacterial antigen Ag85B restrains Hodgkin lymphoma tumor growth by inhibiting autophagy. (PubMed, Oncol Res) - "Mechanistically, Ag85B inhibits autophagy by activating the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase (PI3K/AKT/mTOR) and mitogen-activated protein kinase (MAPK) pathways...Altogether, these results suggest that Ag85B inhibits HL growth via autophagy regulation. Current treatments for HL are associated with adverse events; therefore, Ag85B-mediated autophagy inhibition might be a promising strategy in to treat HL."

Journal • B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • mTOR

Multifunctional Bioactive Dual-Layered Nanofibrous Matrix for Effective Breast Cancer Therapy and Enhanced Wound Healing. (PubMed, Small) - "The HyPhob layer ensures prolonged therapeutic effects by releasing therapeutic molecules, such as rapamycin, enabling sustained chemotherapy (CT) and antibacterial activity...In short, the MBDL-NanoMat platform offers a unique advantage in post-surgical TNBC care by simultaneously targeting tumor recurrence and facilitating wound healing. Further investigation of this platform can significantly improve oncological and regenerative medicine strategies."

Journal • Breast Cancer • Infectious Disease • Oncology • Solid Tumor • Triple Negative Breast Cancer

Combination of Recombinant Methioninase With Rapamycin or Chloroquine Is Synergistic to Highly Inhibit Triple-negative Breast Cancer Cells In Vitro. (PubMed, Anticancer Res) - "rMETase, when combined with either RAPA or CQ, is synergistic on the MDA-MB-231 TNBC cell line. The present findings suggest the potential for future clinical applications of rMETase plus chemotherapy, such as RAPA or CQ, for recalcitrant TNBC."

Journal • Preclinical • Breast Cancer • CNS Disorders • Oncology • Osteosarcoma • Psychiatry • Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Hypoxia-induced autophagy attenuates ferredoxin 1-mediated cuproptosis in colorectal cancer cells. (PubMed, Hum Exp Toxicol) - "In vivo, rapamycin treatment attenuated the tumor-suppressive effects of FDX1 overexpression in nude mouse xenograft models.DiscussionThis study demonstrated that hypoxia-induced autophagy inhibits FDX1-mediated cuproptosis, leading to resistance to copper-induced cell death in CRC cells. Targeting the autophagy pathway may provide a novel therapeutic strategy to overcome resistance to cuproptosis and improving CRC treatment outcomes."

Journal • Colorectal Cancer • Oncology • Solid Tumor • DLAT • FDX1

A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes. (PubMed, J Vis Exp) - "Next, we differentiate monocytes into moDCs, treat them with an established immunomodulator, such as rapamycin, dexamethasone, IL-10, or vitamin D3, for 24 h and test their change in tolerogenic markers as a validation of the protocol. Finally, we co-culture the induced tolDCs with autologous T cells in the presence of anti-CD3/CD28 stimulation and observe changes in Treg populations and T cell proliferation. We envision this protocol being used to evaluate the efficacy of novel immunomodulatory agents to reprogram already differentiated DCs towards tolDC."

Journal • Transplantation • CD14 • IL10

Image-based temporal profiling of autophagy-related phenotypes. (PubMed, Autophagy Rep) - "Therefore, this study acts as proof-of-principle for using image-based temporal profiling to differentiate autophagy perturbations in a high-throughput manner and has the potential identify biologically relevant autophagy phenotypes. Ultimately, approaches like image-based temporal profiling can accelerate drug discovery."

Journal

Rare Case of Tacrolimus-Induced Acute Pancreatitis in a Liver Transplant Recipient. (PubMed, ACG Case Rep J) - "This case highlights the potential for delayed onset of TAP, and we suggest that tacrolimus may warrant reclassification from category III to Ic in the drug-induced pancreatitis classification. In addition, we introduce sirolimus as a viable alternative for immunosuppression following TAP."

Journal • Hepatology • Pancreatitis • Transplantation