Torisel (temsirolimus) / Pfizer - LARVOL DELTA

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

Real-World Practice Patterns of Patient Management in the Peri-CAR T-Cell Therapy Setting for Patients with Mantle Cell Lymphoma: An International Survey on Behalf of the EBMT Lymphoma Working Party (ASH 2024) - "Nearly all (96%) clinicians took into account the impact of bendamustine on T-cell fitness, avoiding it completely (43%) or limiting its use to first-line (53%)...The preferred chemotherapy regimens included R-BAC (35%), R-GEMOX (31%) and cyclophosphamide-based (12%). Alternative regimens, such as R-Lenalidomide, Bortezomib or Temsirolimus, were rarely selected...Conversely, there was a higher use of ongoing single-agent ibrutinib (38% vs 7%) and a similar rate of pirtobrutinib monotherapy (23% vs 26%)...A similar approach was adopted with venetoclax, where a clear majority of participants stopped it prior to LDC (90%); only 1 respondent maintained it after infusion. Conclusion : These findings confirm the current heterogeneity of MCL patient management strategies prior to CAR T-cell therapy and highlight the need to develop consensus guidelines harmonizing the role of BTKi and other targeted molecules across leukapheresis, bridging and infusion."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Interim results confirm the safety and feasibility of autologous hybrid TREG/Th2 T stem cells (RAPA-501) in ALS patients with severe respiratory insufficiency (ALS-MND 2025) - P | " RAPA-501 were manufactured from apheresis products from pwALS using mTORC1/mTORC2 inhibition (temsirolimus) and differentiation cytokines (IL-2, TGF-b, IL-4). Hybrid TREG/Th2 RAPA-501 cells were feasibly manufactured, consistently expressed an effector TREG/Th2 phenotype, and safely administered to pwALS with severe respiratory insufficiency. Pulmonary and disease activity measures were relatively stable post-RAPA-501 therapy, with a potentially favorable overall survival pattern. RAPA-501 T stem cells therefore represents a potentially new approach for therapy of advanced-stage ALS."

Clinical • Amyotrophic Lateral Sclerosis • Inflammation • Respiratory Diseases • CD4 • CD73 • CD8 • FOXP3 • GATA3 • IL2 • IL4 • ITGAE

Dasatinib Overcomes AML Resistance to BCL2 Inhibition By Indirectly Inhibiting MCL1: From Ex Vivo drug Sensitivity/Resistance Profiling to a Phase II Clinical Trial: A Hemato-BIO Study (ASH 2024) - P=N/A | "BH3 mimetics such as the BCL2 specific inhibitor (-inh) venetoclax (VEN) and the BCL2/BLCxL-inh navitoclax (NAV), are small molecules inducing intrinsic apoptotic cell death by inhibiting antiapoptotic proteins...We noticed a strong anticorrelation between NAV-R and sensitivity to most of the tested kinase inhibitors, including the Pi3K-inh BKM120 (Buparlisib) and Idelalisib, the JAK2-inh Ruxolitinib, the MEK-inh Trametinib, the mTOR-inh Temsirolimus, the FLT3-inh Quizartinib, and the BCR-ABL-inh Imatinib and Dasatinib (DASA). On the other hand, we did not observe any anticorrelation with the EGFR-inh erlotinib nor gefitinib...DASA may be efficient in targeting VEN-R by inhibiting MCL1. Preclinical studies based on the AML collections HEMATIO-BIO allowed us to ask clinical questions that can be addressed in early-phase clinical trial."

IO biomarker • P2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCL2 • BCL2L1 • BCR • EGFR • FLT3 • JAK2 • KIT • KRAS • NPM1 • NRAS • PTPN11 • TP53

ARST1431: Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma (clinicaltrials.gov) - P3 | N=325 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Spindle Cell Sarcoma

Myeloperoxidase inhibits prostate cancer progression, suppresses the PI3K/AKT signaling pathway and reshapes the immune microenvironment. (PubMed, Transl Androl Urol) - "Drug sensitivity predictions indicated patients with high MPO expression were more sensitive to PI3K/AKT inhibitors (e.g., temsirolimus), but their TIDE score suggested a potentially lower response to immunotherapy...MPO serves as an independent prognostic marker and its downregulation contributes to tumor growth via PI3K/AKT signaling while influencing the immune microenvironment. These findings suggest MPO as a new target for combined therapeutic strategies based on metabolic intervention."

IO biomarker • Journal • Brain Cancer • Colorectal Cancer • Genito-urinary Cancer • Glioblastoma • Oncology • Prostate Cancer • Solid Tumor • MPO

Trial of Temsirolimus in Patient with Multiple Intestinal Atresia (MIA) and Combined Immunodeficiency (ACAAI 2025) - "Discussion MIA and combined immunodeficiency is a rare genetic disorder with a grave prognosis. The collective expertise of immunologists, allogeneic transplant physicians, and gastroenterologists enabled the use of a creative treatment option, temsirolimus."

Clinical • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pediatrics • Primary Immunodeficiency

Relieving Restriction in Resting CD8+ T Cells Increases Gene Transfer and Improves Tumor Killing after Transduction with CD8-Targeted CD19CAR Fusosome (ASH 2024) - "As part of an effort to increase transduction efficiency, we identified temsirolimus and IL-7 as clinically relevant pharmaceutical agents that lift restriction by IFITM1 and SAMHD1, respectively, in resting CD8+ T cells...Avoiding lymphodepletion and the complexities of autologous CAR T manufacturing makes in vivo delivery of a CD8-targeted CD19CAR fusosome an attractive option for the treatment of B cell malignancies and other B cell-mediated diseases. The findings reported here further our understanding of resting CD8+ T cell transduction, informing the potential use of pharmaceutical interventions or vector modifications to overcome restriction and increase the potency of a CD8-targeted fusosome."

Gene Therapies • Hematological Malignancies • Oncology • CD4 • CD8 • IL7

Efficacy of Neratinib-Based Therapy in ERBB2-Mutant Lung Adenocarcinomas: Findings From 2 International Phase 2 Studies. (PubMed, Clin Lung Cancer) - P2 | "Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients."

Journal • P2 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Tivozanib-Induced Immune Thrombocytopenia in Metastatic Renal Cell Carcinoma: A Case Report and Review (ASH 2024) - "This case report represents one of the initial documented cases detailing the observation of severe Drug-induced immune thrombocytopenia after the initiation of tivozanib treatment in a patient.Case PresentationA 52-year-old male with a history of diabetes mellitus, recent pulmonary embolism on apixaban, and metastatic RCC presented with worsening shortness of breath and hemoptysis three months after initiating tivozanib treatment...Therefore, patient was started on dexamethasone, and intravenous immunoglobulin (IVIG)...However, when tivozanib is used in combination therapies, such as with everolimus or temsirolimus, the incidence of severe thrombocytopenia appears to increase...Testing for drug-specific antiplatelet antibodies can confirm the diagnosis, although this testing may not be widely available.ConclusionIn conclusion, in this case report, we described an incident of tivozanib-induced ITP which suggests that future monitoring of cancer patient placed on TKIs may..."

Case report • Clinical • Metastases • Review • Cardiovascular • Diabetes • Genito-urinary Cancer • Hematological Disorders • Immune Thrombocytopenic Purpura • Metabolic Disorders • Oncology • Pulmonary Embolism • Renal Cell Carcinoma • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Thrombocytopenic Purpura • FLT1

Temsirolimus targets chemoresistant uveal melanoma via mammalian target of rapamycin inhibition and enhances chemotherapy. (PubMed, Anticancer Drugs) - "In this study, we established chemoresistant uveal melanoma cell lines by exposing parental cells to dacarbazine, cisplatin, or gemcitabine and performed high-throughput drug screening incorporating normal human epidermal melanocytes (NHEMs) as a normal control to assess both efficacy and selectivity. Our screening identified temsirolimus and selumetinib as top candidates, with temsirolimus exhibiting strong tumor-selective cytotoxicity...Mechanistically, temsirolimus downregulated mammalian target of rapamycin (mTOR) signaling, as indicated by reduced p-mTOR, p-S6, and p-4EBP1 expression in tumor tissues. These findings demonstrate that temsirolimus selectively targets chemoresistant uveal melanoma cells, enhances chemotherapy efficacy, and suppresses tumor growth via mTOR inhibition, supporting its potential clinical application as a novel therapeutic strategy for chemoresistant uveal melanoma."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • EIF4EBP1

MULTIMODAL MOLECULAR SCREENING OF TUMOR AND CIRCULATING CELL-FREE DNA TO REVEAL THE TUMOR HETEROGENEITY: A CASE OF PARA-TESTICULAR RHABDOMYOSARCOMA. (SIOP 2025) - "The patient was refractory to two chemotherapy lines, and based on our findings, temsirolimus (mTOR inhibitor) was added to target both alterations...Comprehensive mutational tumor profiling is crucial for optimizing therapy by targeting molecular mechanisms and understanding treatment resistance. Non-invasive cf-DNA profiling may guide personalized therapy to improve patient outcomes."

Cell-free DNA • Clinical • Heterogeneity • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor • MET • NF1

DOES MAINTENANCE THERAPY IMPROVE SURVIVAL OF PATIENTS WITH INTERMEDIATE-RISK RHABDOMYOSARCOMA TREATED WITH VAC/VI CHEMOTHERAPY? A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP (SIOP 2025) - "Background and Aims All patients on the ARST1431 intermediate-risk rhabdomyosarcoma (IR-RMS) trial received vinorelbine and cyclophosphamide (VinoC) maintenance for 6 months following 42 weeks of vincristine, dactinomycin, and cyclophosphamide/irinotecan (VAC/VI) ± temsirolimus induction. Addition of VinoC maintenance to VAC/VI induction statistically significantly improved 4-year post-induction EFS and OS, with IPTW-adjusted hazard ratios of 0.61 (95% CI: 0.43–0.86) for EFS and 0.46 (95% CI: 0.28–0.74) for OS. Conclusions Adding VinoC maintenance to VAC/VI induction did not improve the survival of IR-RMS from enrollment compared to VAC/VI alone; however, among patients who completed VAC/VI induction, there was a statistically significant improvement in post-induction survival with the addition of maintenance therapy."

Clinical • Late-breaking abstract • Rhabdomyosarcoma • Sarcoma • Solid Tumor

Prolonged exposure to axitinib alters the molecular profile of Caki-2 renal cell carcinoma cells. (PubMed, Mol Clin Oncol) - "Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki-2 cells, indicating 2.83- and 1.2-fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN-38 compared with Caki-2 cells. Notably, etoposide, 5-fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types...A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP-binding cassette..."

Journal • Genito-urinary Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor • RAC2 • SPHK1 • VEGFD

Targeting mTOR Kinase for Cancer Treatment: A Comprehensive Review With Clinical Insights. (PubMed, Drug Dev Res) - "Key mTOR inhibitors, including rapalogs (e.g., sirolimus, everolimus) and ATP-competitive inhibitors (e.g., MLN0128, PP242), are discussed in detail, along with their clinical applications and limitations. Additionally, we summarize the findings from major clinical trials, including FDA-approved mTOR inhibitors like everolimus and temsirolimus, and non-FDA-approved inhibitors such as sapanisertib and ridaforolimus. The review underscores the importance of understanding mTOR signaling and its role in cancer progression, offering insights into the future of mTOR-targeted therapies in oncology."

Journal • Review • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Cell Carcinoma • Solid Tumor

EFFECTS OF TREATMENT WITH TEMSIROLIMUS VERSUS INTERFERON ALPHA ON SURVIVAL OF PATIENTS WITH METASTATIC RENAL CELL CARCINOMA - SINGLE-CENTER REAL-WORLD EXPERIENCE. (PubMed, Acta Clin Croat) - "In conclusion, temsirolimus therapy had a significantly positive effect on survival in patients with mRCC. Patients treated with temsirolimus showed significantly longer median survival and median PFS compared to patients treated with IFN-alpha."

Clinical • Journal • Real-world evidence • Retrospective data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urology • IFNA1

SenolyticSynergy: An Attention-Based Network for Discovering Novel Senolytic Combinations via Human Aging Genomics. (PubMed, Int J Mol Sci) - "Unlike traditional drug development approaches that rely on randomized screening, research on aging-related pharmaceuticals has employed mechanism-based strategies, resulting in the discovery of the pioneering combination therapy of dasatinib (D) and quercetin (Q)...The combination of temsirolimus and nitazoxanide ranked first and may be the most promising candidate. The analysis of the literature data and computational studies of molecular structures using 3D modeling validated the accuracy of these predictions. This framework paves the way for large-scale research into anti-aging drug combinations, advancing research capabilities in this field."

Journal

Metabolic heterogeneity and survival outcomes in papillary renal cell carcinoma: insights from multi-datasets and machine learning analyses. (PubMed, Hereditas) - "This study revealed the heterogeneity of metabolic molecules in KIRP and established a prognostic machine learning model that enhances risk stratification and may optimize chemotherapy strategies in the management of KIRP."

Biomarker • Heterogeneity • Journal • Tumor mutational burden • Genito-urinary Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor • KIF20A • PYCR1 • TMB

Myosin Light Chain Kinase-Mediated Endothelial Hyperpermeability Underlies Temsirolimus-Induced Lung Injury. (PubMed, FASEB J) - "Mice with systemic and EC-specific MLCK knockout exhibited reduced temsirolimus-induced pulmonary microvascular hyperpermeability and lung injury. Temsirolimus induced pulmonary endothelial hyperpermeability mediated (at least in part) by the Ca2+-dependent MLCK/p-MLC pathway caused EC contraction and contributed to lung injury through mTOR-independent mechanisms."

Journal • Respiratory Diseases • MYLK

A review on mTOR inhibitor use and outcomes of COVID-19 among patients with kidney transplantation. (PubMed, Bioinformation) - "Random-effects models showed that mTOR inhibitors were significantly associated with reduced mortality (OR=0.63, 95% CI 0.48-0.83, P=0.001) but not with COVID-19 severity (OR=0.70, 95% CI 0.41-1.20, P=0.865). Thus, mTOR inhibitors may provide a survival benefit in kidney transplant patients with COVID-19, highlighting the need for further research."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

Efficacy of temsirolimus versus pazopanib in the treatment of advanced renal cell carcinoma: a meta-analysis. (PubMed, Am J Clin Exp Urol) - "Temsirolimus demonstrated greater efficacy in the low-risk group, while pazopanib was superior in the high-risk group for the treatment of RCC. Consideration of both efficacy and toxicity is crucial to guide drug selection for patients. TRN: CRD42024578497 (Registration date: 2024/08/21)."

Journal • Retrospective data • Review • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a N2M2 umbrella trial. (PubMed, Nat Med) - P1/2 | "Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy-alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus-selected according to the best-matching molecular alteration. Patients without matching alterations were randomized between subtrials without strong biomarkers using atezolizumab and asunercept, and the standard of care (SOC), temozolomide...The results of the N2M2 trial support further investigation of temsirolimus in addition to radiotherapy in patients with newly diagnosed glioblastoma with activated mTOR signaling. ClinicalTrials.gov registration: NCT03158389 ."

Journal • P1/2 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

ESFT13: A Phase II Study Evaluating the Addition of Window and Maintenance Therapy to a Standard Chemotherapy Backbone for the Treatment of High-Risk Ewing Sarcoma. (PubMed, Cancers (Basel)) - "ITT did not achieve the prespecified response rate of 50%, according to WHO criteria; however, all patients exhibited decreased volume and metabolic activity, highlighting the limitations of conventional response assessments. Maintenance therapy was feasible and well tolerated. Although limited by small sample size, heterogeneous disease presentations, and the absence of a control arm, this study supports further evaluation of ITT and a maintenance approach in larger, randomized trials for high-risk ES."

Journal • P2 data • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor

Prognostic and therapeutic relevance of IL2RG-related LncRNAs in clear cell renal cell carcinoma. (PubMed, Sci Rep) - "Immune-related pathways were enriched in high-risk patients, and drug sensitivity analysis indicated that high-risk patients were more responsive to sunitinib and temsirolimus. IL2RG and its related 6-IRLs are potential biomarkers for ccRCC progression. The 6-IRLs model provides a robust tool for predicting prognosis and guiding therapeutic decisions."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • IL2 • IL2RG