temsirolimus / Generic mfg. - LARVOL DELTA

Network meta-analysis of second- and later-line therapies in advanced renal cell carcinoma: A comparative effectiveness approach. (ASCO-GU 2026) - "Lenvatinib + everolimus (HR 0.49 vs placebo) and atezolizumab + cabozantinib (HR 0.56 vs placebo) demonstrated the greatest OS benefit. Compared with other active regimens, lenvatinib + everolimus significantly improved OS versus everolimus and temsirolimus monotherapy, ranking highest for OS (P-score = 0.88)...Lenvatinib + everolimus also ranked first for ORR (P-score = 0.94), followed by belzutifan (P-score = 0.86)... In this NMA, lenvatinib + everolimus demonstrated the greatest overall efficacy across OS, PFS, and ORR, outperforming all other therapies except telaglenastat + cabozantinib in PFS. These findings suggest lenvatinib + everolimus as the leading option for second- or later-line therapy in advanced RCC. However, results should be interpreted with caution and warrant confirmation in future large, head-to-head randomized trials."

HEOR • Metastases • Retrospective data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Oncology • Solid Tumor

The potential of mitochondrial permeability transition-driven necrosis-related genes in prognostic evaluation of colorectal cancer patients. (PubMed, Front Oncol) - "Immunoassays revealed that high-risk patients had 9 elevated immune checkpoints, while low-risk patients were more susceptible to pazopanib and temsirolimus. Real-time PCR (RT-qPCR) confirmed low levels of CASP7, PRKCB, and ENDOG mRNA in CRC tissues, with no significant difference between LMNB2 and GZMB. These findings highlight 5 MPTDN-associated prognostic genes in CRC, providing insights for individualized treatment and prognosis."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CASP7 • GZMB • LMNB2 • PRKCB

GSDME-mediated pyroptosis is essential for the chemotherapeutic effects achieved by combined treatment of temsirolimus and 5-fluorouracil in ovarian carcinoma cells. (PubMed, Am J Transl Res) - "GSDME is the principal executor of spontaneous pyroptosis in ovarian cancer tissues. In chemotherapy employing cell cycle-targeting agents or PI3K-AKT-mTOR pathway inhibitors (alone or in combination) is beneficial, and pyroptosis is an indispensable cell death mechanism. Reactive oxygen species act as a nodal regulator orchestrating pyroptosis, apoptosis, and ferroptosis."

Journal • Oncology • Ovarian Cancer • Solid Tumor • GSDMD • GSDME

TORERO: Temsirolimus and Cetuximab in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Gustave Roussy, Cancer Campus, Grand Paris | Unknown status ➔ Completed

Trial completion • Oncology • Solid Tumor

Phase 2b of RAPA-201 Cell Therapy in Post-PD-(L)-1 Melanoma (clinicaltrials.gov) - P2 | N=65 | Not yet recruiting | Sponsor: Rapa Therapeutics LLC | Trial completion date: Sep 2028 ➔ Sep 2029 | Trial primary completion date: Mar 2028 ➔ Mar 2029

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF

A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies (clinicaltrials.gov) - P2 | N=67 | Not yet recruiting | Sponsor: Yonsei University

New P2 trial • Cardiovascular • CNS Disorders • Oncology

In vivo preclinical efficacy of a novel "payload-bearing" peptide LX-101 targeting IGF-1R in Ewing sarcoma (AACR 2026) - "Here, we tested the in vitro and in vivo efficacy of LX-101, a next-generation therapy targeting IGF-1R, which couples a proprietary IGF-1 variant to a cytotoxic MTX payload, as a single agent or in combination with alpelisib (a PI3K inhibitor) and temsirolimus (an mTOR inhibitor) in various ES models. The pharmacodynamic effects were evaluated using a custom tissue microarray (TMA) analysis, using sequential multiplex immunofluorescence of 40 proteins related to the IGF/PI3K/mTOR signaling pathway.Our results indicate that LX-101 exhibits potent single-agent activity in the preclinical setting as an anti-cancer agent for ES, and even stronger activity when combined with agents that inhibit PI3K or mTOR. Collectively, the preclinical efficacy demonstrated provides a strong rationale for advancing LX-101 into clinical trials for ES."

Preclinical • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IGF1

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

High-throughput drug screening and single-cell network analysis identify rational combination therapies in IDH-mutant glioma (AACR 2026) - "For example, we found that AC-like cells may first be primed with the mTOR inhibitor temsirolimus to reprogram them toward a more drug-sensitive OC-like state, thereby converting a resistant lineage into one that is more vulnerable, including to the new class of IDH1 inhibitors. A second-line agent such as the HDAC inhibitor romidepsin or the topoisomerase inhibitor irinotecan can then be used, possibly in combination with IDH1 inhibitors, to target the resulting OC-like and pre-existing OC/NPC cells, thus implementing a two-step, sequential treatment strategy...Single-cell and spatial transcriptomic profiling (10x Genomics Xenium) of treated slices will map the reprogramming and elimination of malignant subpopulations in situ. Together, this framework provides a blueprint for discovering state-specific dependencies in IDH-mutant glioma and for guiding rational, combination-based strategies to overcome intratumoral heterogeneity."

Combination therapy • Brain Cancer • Glioma • Oncology • Solid Tumor • IDH1

A phase I study of temsirolimus in combination with metformin in patients with advanced or recurrent endometrial cancer. (PubMed, Gynecol Oncol) - P1 | "The results of this single-center clinical trial showed that, in patients with advanced or recurrent endometrial cancer, metformin can be safely added to temsirolimus providing limited response without added safety concerns."

Journal • P1 data • Anorexia • Dyslipidemia • Endometrial Cancer • Fatigue • Hematological Disorders • Hypertriglyceridemia • Mucositis • Oncology • Renal Disease • Solid Tumor • Thrombocytopenia

USP14 inhibitor IU1 alleviates amyloid-β mediated toxicity in Alzheimer's disease cell and worm models. (PubMed, J Alzheimers Dis) - "Notably, autophagy activators, including mTOR inhibitors rapamycin, everolimus, and temsirolimus, worsened Aβ toxicity. Conversely, autophagy inhibitors such as Bafilomycin A and chloroquine reduced APP-C99/Aβ accumulation, enhanced proteasomal activity, decreased cell death, and improved neurodegeneration and behavior in the worm model.ConclusionsThis study reveals that, under Aβ-mediated proteostasis dysfunction, autophagy activation exacerbates toxicity, whereas proteasome activation via allosteric inhibition of USP14 using IU1 was neuroprotective. These findings provide evidence to suggest that targeting proteasome stimulation via pharmacological inhibition of USP14 offers a promising therapeutic strategy for AD."

Journal • Alzheimer's Disease • CNS Disorders • Targeted Protein Degradation • APP • USP14

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) (clinicaltrials.gov) - P2 | N=720 | Recruiting | Sponsor: Canadian Cancer Trials Group | Trial primary completion date: Jan 2026 ➔ Dec 2026

Pan tumor • Trial primary completion date • Tumor mutational burden • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • BRAF

Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer (clinicaltrials.gov) - P1 | N=38 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor • PIK3CA • PTEN

Enzymatic C42 Diversification of Rapamycin Identifies a Potent Butyryl-Modified Anticancer Derivative. (PubMed, Org Lett) - "Biological screening identified derivative 9 as a potent lead compound with superior antiproliferative activity (IC50 = 6.5 μM in ACHN cells), outperforming both rapamycin and temsirolimus. This work offers a practical enzymatic route for rapamycin remodeling and highlights a promising mTOR-targeted anticancer candidate."

Journal • Oncology

Implantable Microdevice for the Delivery of Drugs and Their Effect on Tumors in Patients With Metastatic or Recurrent Sarcoma (clinicaltrials.gov) - P=N/A | N=20 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2025 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Development and validation of a herb-related gene signature for prognosis prediction and therapeutic response assessment in breast cancer. (PubMed, Transl Cancer Res) - "Furthermore, the signature identified several compounds (e.g., sirolimus, temsirolimus) with potential heightened sensitivity in high-risk patients. This study developed and validated a novel TCM-derived gene signature that reliably stratifies breast cancer patients into distinct risk groups and is independently prognostic. While its clinical utility requires extensive validation in prospective studies before it can inform patient management, this novel gene signature may serve as a potential tool for individualized risk assessment and prognosis prediction, while also generating compelling hypotheses for guiding immunotherapy and targeted therapy strategies, contributing to the ongoing exploration of precision oncology in breast cancer."

Gene Signature • IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor

Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (ASH 2023) - P | "In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7RALT), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3KALT)...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • ATM • BCL2 • DNMT3A • IDH1 • IDH2 • IL7R • PHF6 • SRSF2 • TET2 • TP53

Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. (PubMed, Haematologica) - P1/2 | "ORR for cHL patients in the exploratory cohort, most of whom had relapsed after both brentuximab vedotin and ASCT, was 80% (35% CR). Combination therapy with TEM/LEN was feasible and demonstrated encouraging activity in heavily-pretreated lymphomas, particularly in relapsed/refractory cHL. ClinicalTrials.gov identifier: NCT01076543."

Clinical • Journal • P1/2 data • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

N2M2/NOA-20: Phase I/IIa umbrella trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation. (ASCO 2024) - P1/2 | "Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ)...The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug... N 2 M 2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • CDKN2A • CDKN2B

Multi-omics integrative analysis of stemness-associated pathological signatures to guide prognosis and therapeutic strategies in uveal melanoma. (PubMed, Int J Surg) - "This study highlights a novel integrative framework combining pathomics and scRNA-seq to decode stemness-driven heterogeneity in UVM. The IPS model offers a non-invasive tool for risk stratification and therapeutic guidance, paving the way for precision oncology in rare ocular malignancies. Notably, the IPS was derived and internally validated within a single TCGA-UVM cohort, and its generalizability to other populations requires validation in independent multi-center cohorts."

IO biomarker • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Temsirolimus (T) in patients (pts) with solid tumors with mTOR mutation: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. (ASCO 2022) - P2 | "Monotherapy T showed evidence of anti-tumor activity in pts with advanced solid tumors with mTOR mut. Additional study is warranted to confirm the efficacy of T in pts with mTOR mut."

Clinical • Acute Kidney Injury • Biliary Cancer • Diabetes • Dyslipidemia • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Hepatology • Hypertension • Hypertriglyceridemia • Inflammation • Leukopenia • Mucositis • Nephrology • Oncology • Pneumonia • Renal Disease • Solid Tumor • Thrombocytopenia • Uterine Cancer • mTOR

Temsirolimus (T) in patients (pts) with solid tumors with PTEN mutation (mut): results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study (AACR 2023) - "T met prespecified criteria to declare a signal of activity in pts with solid tumors with PTEN mut.Table: Baseline Characteristics (N=34); Efficacy Outcomes (n=27); Toxicity Outcomes (N=34) Median (Med) age, years (range) 65 (42, 84)Female, % 14 (41)ECOG PS, % 0 13 (38) 1 18 (53) 2 3 (9)Prior systemic regimens, % 1 3 (9) 2 5 (15) ≥3 26 (77)DC rate, % (OR and SD16+) (1-sided 90% CI) 26 (15.1, 100)OR rate, % (95% CI) 7 (1, 24)Med PFS, wks (95% CI) 10 (7, 17)Med OS, wks (95% CI) 32 (13, 42)DOR, wks (n=2) 11 and 55Med duration SD, wks (n=5) 27 (24, 36)Number of pts1 with tx-related grade 3-4 AE or SAE AE2  12 (35) SAE3 6 (18)1Pts may have experienced one or more events 2 alkaline phosphatase increase, anemia, chronic kidney disease, diarrhea, fatigue, hyperglycemia, hypokalemia, hypophosphatemia, lung infection, oral pain and all SAEs3 acute kidney injury, dyspnea,..."

Clinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • PTEN

Iatrogenic Kaposi Sarcoma Revealed by Acral Nodules With Silent Pulmonary Involvement in Two Patients Treated for Autoimmune Blistering Diseases. (PubMed, Cureus) - "Corticosteroids were tapered and discontinued, and temsirolimus 25 mg IV weekly was initiated with antihistamine and dexamethasone premedication. Clinicians should maintain a high index of suspicion for Kaposi sarcoma in immunosuppressed patients presenting with new acral lesions. Prompt biopsy, staging, steroid tapering, and consideration of mTOR inhibitors may support disease control."

Journal • Dermatology • Epstein-Barr Virus Infections • Immunology • Kaposi Sarcoma • Melanoma • Oncology • Pain • Sarcoma • Solid Tumor • Transplantation

Computer prediction and genetic analysis identifies retinoic acid modulation as a driver of conserved longevity pathways in genetically diverse Caenorhabditis nematodes. (PubMed, Elife) - "While 11 compounds (aldosterone, arecoline, bortezomib, dasatinib, decitabine, dexamethasone, erlotinib, everolimus, gefitinib, temsirolimus, and thalidomide) either had no effect on median lifespan or were toxic, 5 compounds (all-trans retinoic acid, berberine, fisetin, propranolol, and ritonavir) extended lifespan in Caenorhabditis elegans. While the canonical Akt-target FOXO/DAF-16 was largely dispensable, other conserved Akt-targets (Nrf2/SKN-1 and HSF1/HSF-1), as well as the conserved catalytic subunit of AMPK AAK-2, were all necessary for longevity extension by atRA. Our results highlight the potential of combining computational prediction of longevity interventions with the power of nematode functional genetics and underscore that the manipulation of a conserved metabolic regulatory circuit by co-opting endogenous signaling molecules is a powerful approach for discovering aging interventions."

Journal • AKT1 • AKT2 • AMPK • HSF1