sirolimus / Generic mfg. - LARVOL DELTA

Non-Melanoma Skin Cancer Risk Among Transplant Patients: A Large Real-World Comparison of Immunosuppressive Regimens (AAD 2026) - "Recent reports suggest that azathioprine may increase the risk of NMSC compared with alternatives, but direct comparative evidence in large real-world populations remains limited.1-2 We conducted a retrospective analysis using the TriNetX Research Network, encompassing more than 275 million patients across 120 healthcare organizations...In contrast, no meaningful differences in NMSC incidence were found among cyclosporine, tacrolimus, sirolimus, or everolimus monotherapy, with comparable event rates and overlapping confidence intervals across all comparisons...For dermatologists involved in post-transplant care, recognizing how immunosuppressive selection influences NMSC burden is critical for tailoring surveillance, counseling, and interdisciplinary management. By integrating real-world data, this study provides practical evidence to guide both dermatologists and transplant clinicians in balancing graft preservation with skin cancer prevention in this high-risk population."

Clinical • Real-world • Real-world evidence • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Organ Transplantation • Solid Tumor • Transplantation

Reduced-Dose Rabbit Anti-Thymocyte Globulin for GVHD Prophylaxis Following Haploidentical Peripheral Blood Stem Cell Transplantation with Reduced-Intensity Conditioning: A Single-Center Retrospective Analysis (HOPA 2026) - "Post-transplant cyclophosphamide (PTCy) has improved outcomes in haploHSCT by reducing GVHD incidence while preserving survival; however, rates of acute and chronic GVHD remain as high as 41% and 31%, respectively...Banner MD Anderson Cancer Center (BMDACC) utilizes a novel GVHD prophylaxis regimen combining PTCy, tacrolimus, sirolimus, and reduced-dose, non-pharmacokinetically driven rATG (1 mg/kg) administered as a single dose on day +5 post-haploHSCT following RIC...RIC regimens consisted of fludarabine and melphalan (70-140 mg/m2), with or without thiotepa (2.5-10 mg/kg)...Exclusion criteria included prior alloHSCT, prior autologous HSCT within two years, receipt of abatacept, or left ventricular ejection fraction (LVEF) <45% at the time of transplant, which would preclude PTCy utilization... To be determined upon study completion."

Preclinical • Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Myelofibrosis • Transplantation

Evaluation of Ruxolitinib for Graft Versus Host Disease (GVHD) Prophylaxis in Pediatric Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients Intolerant to Initial Prophylactic Regimens (HOPA 2026) - "GVHD prophylaxis typically consists of a calcineurin inhibitor (CNI) or sirolimus combined with methotrexate or mycophenolate mofetil. Pending"

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Nephrology • Pediatrics • Transplantation

Identification of risk factors for tacrolimus intolerance and its impact on outcomes in allogeneic stem cell transplant recipients (HOPA 2026) - "Background Graft-versus-host disease (GVHD) is reported in 20-80% of allogeneic stem cell transplant (alloSCT) recipients and is a major cause of morbidity and mortality, with 1-year mortality rates exceeding 30%.1,2 GVHD prophylaxis with a calcineurin inhibitor (CI) in combination with methotrexate or cyclophosphamide and mycophenolate is considered the standard of care to decrease the risk of severe GVHD...At the Hospital of the University of Pennsylvania (HUP), sirolimus is used as an alternative GVHD prophylaxis agent in patients who develop tacrolimus intolerance or have risk factors that caution its use...Results Pending. Conclusion/Discussion Pending."

Clinical • Chronic Kidney Disease • CNS Disorders • Genetic Disorders • Graft versus Host Disease • Immunology • Nephrology • Polycystic Kidney Disease • Transplantation

A novel pH-sensitive probe to quantify autophagy on high throughput/content imaging platforms (AACR 2026) - "Human cervical carcinoma HeLa cells, and mutants RB1CC1-/- (FIP200) and ATG5-/- were induced for autophagy with rapamycin, torin-1 and serum deprivation and inhibited with 3-methyladenine, MRT68921, chloroquine and bafilomycin A1. Pixel co-localization analysis demonstrated significant overlap between CalRexinTM:pHrodoTM Red and markers of early and late endosomes, as well as LysoTrackerTM, a marker of autolysosomes.CalRexinTM:pHrodoTM Red is accumulated via the endosome-amphisome-autolysosome (low pH ~4.5) pathway, thus connecting to canonical autophagy and yielding a bright fluorescent signal. CalRexinTM:pHrodoTM Red provides a novel approach for imaging autophagy on high throughput/content platforms and is adaptable for screening large chemical libraries for the identification of novel autophagy-modulators as potential drugs for treatment of chronic diseases."

Cervical Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • ATG5 • RB1CC1

High-content morphology profiling identifies autophagy-modulating compounds and their off-target activities (AACR 2026) - "The Cell Painting assay offers this possibility: by capturing rich morphological snapshots, it lets us see how different compounds alter organelles and pathways involved in autophagy. We exposed HepG2 cells for 24 hours to several well-characterized autophagy inhibitors—chloroquine, bafilomycin A1, dauricine, daurisoline, and dorsomorphine—as well as two established activators, rapamycin and PP242. Cell Painting proved effective at distinguishing autophagy-modulating compounds through their characteristic organelle-level effects. The unexpected behaviour of MCOPPB highlights a previously overlooked mechanism. Combining morphological profiling with marker-based validation provides a practical framework for identifying new modulators of autophagy with potential oncological relevance.This work was supported by the Technology Agency of the Czech Republic project PERMED: T2BA (TN02000109)."

Oncology • SQSTM1

The mystery behind mSin1 phosphorylation (AACR 2026) - "Collectively, our findings suggest that that rapamycin inhibits mSin1 phosphorylation by targeting a novel mTOR complex and might be associated with glucose metabolism in some contexts. Further research is needed to define the exact phosphorylation sites and their significance as well as the new mTOR complex regulating these phosphorylation sites."

Oncology

Intermittent Fasting and Androgen Receptor Signaling in Prostate Cancer: Metabolic Crosstalk and Therapeutic Implications. (PubMed, Int J Mol Sci) - "Mechanistically, IF-induced metabolic stress engages AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and sirtuin pathways, alters lipid and mitochondrial metabolism, and transiently increases reactive oxygen species (ROS), creating vulnerabilities in prostate tumor cells. Translational evidence suggests potential benefits of integrating IF with standard therapy, but effects may depend on fasting regimen, caloric intake, macronutrient composition, and patient metabolic context, including risk of lean mass loss. This review highlights the metabolic crosstalk between IF and AR signaling and emphasizes the need for future clinical studies incorporating biomarker-guided approaches and body composition monitoring to fully exploit this intersection for improved therapeutic outcomes in prostate cancer."

Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AMPK • IGF1 • mTOR

PTPN2 alleviates psoriasis by targeting the STING-STAT3 axis and restoring autophagy: in vitro and in vivo evidence. (PubMed, Immunobiology) - "Using cellular and imiquimod-induced mouse models, we assessed PTPN2 expression and function using multiple techniques, including immunofluorescence, co-immunoprecipitation, and Western blotting...PTPN2 overexpression attenuated psoriatic pathology, and this therapeutic benefit was further enhanced by co-administering the autophagy inducer rapamycin. Collectively, our results delineate a novel mechanism by which PTPN2 alleviates psoriasis-like pathology in keratinocytes by targeting the STING-STAT3 pathway and promoting autophagy and apoptosis. These findings indicate that PTPN2 is a potential therapeutic target, with in vivo validation supporting its translational relevance."

Journal • Preclinical • Dermatology • Dermatopathology • Immunology • Oncology • Psoriasis • IL17A • PTPN2 • STING • TNFA

Cell-intrinsic mTOR/LET-363 influences morphological aging of the ALM touch receptor neuron in Caenorhabditis elegans. (PubMed, PLoS One) - "The mechanistic target of rapamycin (mTOR) promotes neuronal aging, but it remains unclear whether these effects arise from mTOR activity within neurons, other brain cell types, or peripheral tissues...Together, these findings suggest that mTOR/let-363 can act cell-intrinsically within neurons to promote or potentiate an aspect of morphological aging. These results help clarify the potential cell-type specificity of mTOR's roles in neuronal aging and provide a foundation for defining the mechanisms through which mTOR intersects with neuron-intrinsic aging pathways."

Journal

Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy. (PubMed, Molecules) - "Classical autophagic activators (e.g., rapamycin) can initiate upstream steps in the pathway but cannot address downstream flux bottlenecks, limiting their ability to restore effective TDP-43 clearance. This review revisits classical strategies and discusses newer approaches to modulate TDP-43 clearance, including transcription factor EB (TFEB) activators, proteolysis-targeting chimeras (PROTACs), and antisense oligonucleotides (ASOs). We propose that adopting multi-targeting strategies and developing better biomarkers are vital for clinical success."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Proteinopathy • Targeted Protein Degradation • TARDBP • TFEB

Colon-restricted Pten haploinsufficiency models PI3K pathway-driven invasion in colorectal cancer. (PubMed, Cell Mol Gastroenterol Hepatol) - "The effect of Pten haploinsufficiency on colonic tumor formation in mice reaffirms the significance of PI3K alterations in tumor evolution in human colorectal cancers."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • PI3K • PTEN

mTOR enables alveolar macrophage survival and GM-CSF-STAT5-PPARγ signaling: Genetic and temsirolimus evidence (AACR 2026) - "Mechanistic target of rapamycin (mTOR) inhibitors, widely used in transplant and oncology settings, can induce a noninfectious pneumonitis linked to disrupted alveolar macrophage (AM) function. In contrast, mTOR-deficient AM-like cells failed to upregulate p70 S6 kinase, C/EBPβ, PPARγ, CD36, MerTK, Bcl-2, and Bcl-xL. Rapamycin impaired survival of wild-type AM-like cells in a dose-dependent manner, partially rescued by increasing GM-CSF.Together, these findings identify mTOR as a non-redundant regulator of GM-CSF survival signaling in AMs—a dependency absent in IMs—supporting an AM mechanism for mTOR inhibitor-associated alveolar injury."

IO biomarker • Oncology • BCL2 • BCL2L1 • CD36 • CSF2 • ITGAX • JAK2 • MERTK • MRC1 • PPARG • SCARB1 • STAT5 • STAT5AWqe

Combination Therapy (Mirdametinib and Sirolimus) for RAS Mutated Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=54 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Hematological Malignancies • Multiple Myeloma • Oncology • KRAS • NRAS

Hepatic Epstein-Barr Virus–Associated Smooth Muscle Tumors: Insights from a Multi-Institutional Cohort (USCAP 2026) - "Patient management varied based on underlying disease status and included antiretroviral therapy, reduction of immunosuppression in transplant recipients, radiation, sirolimus, rituximab, or surgery. Hepatic EBV-SMTs are rare tumors predominantly affecting young immunocompromised patients. Despite frequent multifocality, outcomes are generally favorable, with multiple lesions thought to represent separate primaries rather than metastasis. Given their morphologic overlap with other spindle cell neoplasms, accurate recognition is essential to prevent misdiagnosis and unwarranted therapy."

Clinical • Epstein-Barr Virus Infections • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leiomyosarcoma • Oncology • Pneumonia • Respiratory Diseases • Sarcoma • Solid Organ Transplantation • Solid Tumor • Spindle Cell Sarcoma

ST2 enforces a 'repair-ready' Treg phenotype that homes to and ameliorates neuroinflammation. (IMMUNOLOGY 2026) - "Improvements often address singular issues and fail to engender 'repair-ready' cells. We developed GNTI-823, an engineering strategy to generate Tregs (EngTreg) from human CD4 T cells that constitutively express FOXP3 for stability and scalability; contain a rapamycin-activated chemically induced IL-2 signaling complex (CISC) for persistence; and express the IL-33-responsive alarmin receptor ST2 for inflammatory-homing and in vivo functionality. ST2 expression successfully conferred a 'Tissue' Treg phenotype, characterized by high expression of inflammatory homing receptors, metabolic genes and tolerogenic factors absent from non-ST2 EngTregs or circulating Tregs... Thus, GNTI-823 EngTregs are designed to home, function and persist in neuroinflammatory sites, which show pre-clinical promise for the treatment of ischemic stroke and other neuroinflammatory and degenerative conditions."

Cardiovascular • Inflammation • Ischemic stroke • CD4 • FOXP3 • IL2 • IL33 • ST2

An allogeneic CD19 targeted Engineered Treg approach for treating B cell mediated autoimmune diseases (IMMUNOLOGY 2026) - "Introduction/Rationale: CD19 CAR T cells have demonstrated promising efficacy in SLE by deeply depleting B cells, but these autologous cell therapies are expensive to deploy, come with significant toxicity risks, and lack the ability to control additional immune cell functions driving autoreactive B cell generation and lupus pathogenesis. We developed GNTI-350, an allogeneic hypoimmune CD19 CAR–engineered regulatory T cell (CAR19 EngTreg) therapy, which leverages stable FOXP3 expression, a CD19 CAR for selective targeting, and a rapamycin-inducible IL-2 signaling complex to sustain Treg function. Persistence of GNTI-350 is enabled by Immune Evasion Engineering (IEE), a hypoimmune technology that allows MHC-deficient allogeneic cell therapies to evade host NK cell clearance. These data show that GNTI-350 can safely achieve a durable immune reset and may provide superior therapeutic benefit over CAR-T approaches to patients with B cell–driven autoimmune diseases."

IO biomarker • Immunology • Inflammatory Arthritis • Lupus • CD19 • FOXP3 • IL2

Inhibition of Innate Immune Allorecognition Using Nanobiologics Effectively Overturns Ongoing T Cell Mediated Allograft Rejection (IMMUNOLOGY 2026) - "Nanobiologics were either unloaded (control; U-NB) or loaded with the mTOR inhibitor rapamycin (mTORi-NB; 5mg/kg) and compared to free rapamycin (Rapa; 5mg/kg). We uncovered that Allo-IMem signals through mTOR, and unlike Rapa treatment, mTORi-NB inhibits Allo-IMem compared to U-NB... Taken together, we demonstrate that inhibiting Allo-IMem using innate cell specific mTORi-NB effectively overturns TCMR, thus providing a novel targeted therapeutic treatment for acute rejection in transplant patients."

Transplant Rejection • IFNG • TGFB1

Lysosomal solute carriers promote pro-inflammatory signaling and MHC-II antigen presentation in dendritic cells (IMMUNOLOGY 2026) - "We have analyzed cytokine secretion by ELISA, transcription factor nuclear translocation by subcellular fractionation and RNA seq, Ag presentation and T cell activation by flow cytometry and biochemical assays, and calcium measurements by live-cell imaging. We have found that the histidine transporter SLC15A4 promotes pro-inflammatory responses by activating the master regulator of cell fitness, mechanistic target of rapamycin complex 1 (mTORC1). Our findings suggest that SLC15A4 and SLC29A3 regulate phagosomal signaling in murine dendritic cells via differential mechanisms to promote anti-bacterial immunity while preventing excessive inflammation."

Inflammation

Nicotine Reprograms Macrophage Autophagy to Drive Pro-Inflammatory Lung Immunity (IMMUNOLOGY 2026) - "Autophagy flux was modulated with rapamycin or bafilomycin A1, and autophagy markers (LC3B, p62, Beclin-1) were quantified by Western blot. Nicotine impaired macrophage autophagic flux, evidenced by p62 accumulation, reduced Beclin-1, and increased LC3B-II levels, consistent with defective autophagy turnover... These findings identify nicotine as a mechanistic driver of macrophage accumulation, inflammatory polarization, and lung immune dysregulation, and suggest macrophage autophagy as a potential therapeutic target"

Inflammation • Pneumonia • BECN1 • CSF2 • IL17A • IL1B • IL23A • IL6

Short-term rapamycin treatment of an older human cohort alters immune and inflammatory markers but fails to re-set the epigenetic biological clock (IMMUNOLOGY 2026) - "Introduction/Rationale: Pharmacological inhibition of the mTOR pathway with rapamycin (RAPA) extends lifespan and improves aspects of healthspan in mice. Although many RAPA effects could be elicited by short-term inhibition of mTOR, other parameters will likely require a longer treatment. To explore this possibility, we were recently funded for a PK/PD analysis of mTOR inhibition in older humans. The goal is to identify the optimal drug (RAPA vs."

Inflammation • FOXP3 • ITGAM

The rapamycin sTORy: 50-year journey from Easter Island to the frontiers of biology and medicine. (PubMed, Trends Biochem Sci) - "What began as the characterization of a natural product led to the identification of an entirely new signaling cascade, the target of rapamycin (TOR) pathway, and the emergence of a new field in biomedical research. Here, we review the historical and molecular foundations of the TOR field, from the discovery of rapamycin to current models of nutrient sensing, pathway regulation, clinical applications, and future perspectives."

Journal • Review

Rapamycin reduces peritendinous fibrosis but has a limited effect on intratendinous healing in a rodent Achilles tendon injury model. (PubMed, Sci Rep) - No abstract available

Journal • Preclinical • Fibrosis • Immunology

The mTOR pathway in pristane -induced lupus models (IMMUNOLOGY 2026) - "These findings indicate the activity of mTOR, the central regulator of metabolic reprogramming, in myeloid cells influences the clinical phenotype of SLE."

Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • SDC1

CCL20-CCR6 signaling modifies cellular metabolism in CD4 T cells and drives the differentiation of pathogenic Th17 cells (IMMUNOLOGY 2026) - "This pathway triggers rapamycin-sensitive phosphorylation events involving PI3K, Akt, mTORC1, and STAT3, contingent on CCR6 expression. Our results suggest that changes in Th17 metabolism triggered by CCR6 offer a promising avenue for developing a therapeutic strategy to control gut inflammation and autoimmunity."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • CCL20 • CCR6 • CD4 • IL17A • IL2RA • PI3K • RAG1 • STAT3