EC359 / Evestra - LARVOL DELTA

Investigating the potential of EC359 in inducing ferroptosis for the treatment of type I and type II endometrial cancers (AACR 2025) - "In conclusion, our data indicate that EC359 is a potent inducer of ferroptosis in endometrial cancer cells and has the potential to be used as an additional tool in current endometrial cancer treatment regimens."

Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • LIFR

Low-grade serous ovarian cancer is effectively treated with a combination of trametinib and LIFR inhibitor therapeutics (AACR 2025) - "These results indicate that the EC359 + trametinib combination therapy may provide a promising therapeutic approach for the treatment of LGSOC by enhancing the efficacy of trametinib and targeting critical signaling pathways."

Gynecologic Cancers • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS • LIFR • STAT3

Targeting the LIF/LIFR axis reduces the progression of inflammatory breast cancer by promoting ferroptosis (AACR 2025) - "Collectively, our research suggests that the inhibition of LIFR promotes ferroptosis-mediated cell death in IBC, and LIFR inhibitors represent a novel therapeutic option for IBC."

Breast Cancer • Inflammatory Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • GPX4 • LIFR • SLC7A11

Targeting the Leukemia Inhibitory Factor/Leukemia Inhibitory Factor Receptor Axis Reduces the Growth of Inflammatory Breast Cancer by Promoting Ferroptosis. (PubMed, Cancers (Basel)) - "EC359 (5 mg/kg/day) was effective in reducing the growth of the IBC KPL4 xenograft tumors. These findings demonstrates that LIFR inhibition promote ferroptosis-mediated cell death in IBC and that EC359 represent novel therapeutic for IBC treatment."

Journal • Breast Cancer • Hematological Malignancies • Inflammatory Breast Cancer • Leukemia • Oncology • Solid Tumor • GPX4 • LIF • LIFR

Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer. (PubMed, Cancers (Basel)) - "RNA-Seq analysis identified critical pathways modulated by LIF/LIFR signaling in diet-induced obesity mouse models. These findings suggest that adiposity contributes to TNBC progression via the activation of the LIF/LIFR pathway, and LIFR inhibition with EC359 represents a promising therapeutic approach for obesity-associated TNBC."

Journal • Breast Cancer • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology • Solid Tumor • Triple Negative Breast Cancer • LIF • LIFR

Leukemia Inhibitory Factor Receptor inhibition by EC359 reduces atherosclerotic stenosis grade in Ldlr-/- mice. (PubMed, Eur J Pharmacol) - "Consequently, immune cell infiltration was reduced in aortic plaques of EC359 treated mice compared to control mice. Conclusively, we demonstrated that LIF receptor is a potential therapeutic target in atherosclerosis by reducing plaque size, attributed to lower serum cholesterol levels, reduced endothelial activation and less immune cell infiltration in the plaque."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Malignancies • Leukemia • Oncology • CD31 • IL6 • LIF • LIFR • PECAM1 • VCAM1

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis. (PubMed, NPJ Precis Oncol) - "Additionally, EC359 therapy considerably improved tumor immunogenicity by robust CD45+ leukocyte tumor infiltration and polarizing tumor-associated macrophages (TAMs) toward M1 phenotype while showing no impact on normal T-, B-, and other immune cells. Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa."

Journal • Colorectal Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR • PTPRC

Pharmacological inhibition of the LIF-LIFR autocrine loop reveals vulnerability of ovarian cancer to ferroptosis (AACR 2024) - "Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa."

Colorectal Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • LIF • LIFR • PTPRC

Significance of LIF/LIFR axis in the progression of inflammatory breast cancer (AACR 2024) - "Collectively, these studies demonstrated the therapeutic benefit of using EC359 to target the LIF/LIFR axis and opened the door for the development of new treatment approaches."

Breast Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL6 • LIF • LIFR

EC359, A new therapeutic drug for the treatment of low grade serous ovarian cancer (AACR 2024) - "EC359 enhanced the efficacy of trametinib, a currently used medication of LGSOC. Together, our findings support the existence of LIF/LIFR autocrine loops, and EC359 is a viable treatment option for LGSOC."

Colorectal Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS • LIF • LIFR • STAT3

Leukemia inhibitory factor (LIF)-factor XIIIA mediated macrophage-stromal crosstalk in pancreatic cancer (AACR 2024) - "This study delves into the potential regulatory pathway through which LIF induces remodeling of the ECM within the PDAC TME. We targeted LIF-induced macrophage-stromal crosstalk using the LIFR antagonist (EC359) in an orthotopically tumor implanted LSL-KrasG12D/+; Trp53 R172H/+; Pdx1Cre/+ (KPC) mice model of PDAC... Our investigation provides valuable insights into the possible mechanism by which LIF triggers ECM remodeling, thereby contributing to the desmoplastic stroma. Significantly, our findings propose that LIF-regulated FXIIIa signaling in macrophages serves as a plausible mediator of the LIF-induced ECM remodeling in PDAC."

Stroma • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • F13A1 • KRAS • LIF • LIFR • TP53

The LIFR Inhibitor EC359 Effectively Targets Type II Endometrial Cancer by Blocking LIF/LIFR Oncogenic Signaling. (PubMed, Int J Mol Sci) - "Tumor progression was markedly inhibited by EC359 treatment in two different patient-derived xenograft models in vivo and patient-derived organoids ex vivo. Collectively, these results suggest LIFR inhibitor EC359 as a possible new small-molecule therapeutics for the management of Type II ECa."

Journal • Endometrial Cancer • Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • LIF • LIFR • STAT3

The LIFR-targeting small molecules EC330/EC359 are potent ferroptosis inducers. (PubMed, Genes Dis) - No abstract available

Journal • LIFR

Targeting leukemia inhibitory factor in pancreatic adenocarcinoma. (PubMed, Expert Opin Investig Drugs) - "Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients."

IO biomarker • Journal • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • IL6

Targeting LIF/LIFR autocrine loops with EC359 in ovarian cancer: A novel LIFR targeted therapy (AACR 2023) - "Together, our findings support the existence of LIF/LIFR autocrine loops, and EC359 is a viable treatment option for OCa."

Gynecologic Cancers • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • ITGAM • LIFR • PTPRC • STAT3

The role of obesity in promoting the LIF/LIFR signaling in triple negative breast cancer (AACR 2023) - "Collectively, these findings suggest that obesity conditions promote the activation of LIF/LIFR pathway, which in turn enhances TNBC cell proliferation. The LIFR inhibitor EC359 may be employed as a new therapeutic drug to treat obesity driven TNBC and LIF/LIFR axis represents a potential therapeutic target for obesity driven TNBC."

Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • LIFR • STAT3

Inhibition of LIFR Blocks Adiposity-Driven Endometrioid Endometrial Cancer Growth. (PubMed, Cancers (Basel)) - "Further, treatment with EC359 significantly attenuated adipocyte-induced EEC progression in vivo. Collectively, our data support the premise that LIF/LIFR signaling plays an important role in obesity-driven EEC progression and the LIFR inhibitor EC359 has the potential to suppress adipocyte-driven tumor progression."

Journal • Endometrial Cancer • Genetic Disorders • Hematological Malignancies • Leukemia • Obesity • Oncology • Solid Tumor • LIFR

Next-Generation Sequencing Analysis of Gastric Cancer Identifies the Leukemia Inhibitory Factor Receptor as a Driving Factor in Gastric Cancer Progression and as a Predictor of Poor Prognosis. (PubMed, Front Oncol) - "These effects were reversed by the pharmacological blockade of LIFR signaling. Together, these data suggest that LIFR might have a major role in promoting disease progression and peritoneal dissemination in patients with GC and that development of LIF/LIFR inhibitors might have a role in the treatment of GC."

Biomarker • Journal • Next-generation sequencing • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Peritoneal Cancer • Solid Tumor • CDH1 • IL6 • LIFR • VIM

"played it yet? @KCzaicki @NiftyAngel61 @ClintonQuerry @Venefi5 @pedocoll @Otaa_ @ademastomas @llemk1wins @katec359 @BatangAnghell @CityNobu @admira12345 @Jessica43347771 @mmirsae" (@AudraMa19047748)

The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights. (PubMed, Biochim Biophys Acta Rev Cancer) - "This review article provides an overview of the structure and ligands of LIFR, LIF/LIFR signaling in developmental biology, stem cells, cancer stem cells, genetics and epigenetics of LIFR, LIFR regulation by long non-coding RNAs and miRNAs, and LIF/LIFR signaling in cancers. Finally, neutralizing antibodies and small molecule inhibitors preferentially blocking LIF interaction with LIFR and antagonists against LIFR under pre-clinical and early-phase pre-clinical trials were discussed."

Journal • Review • Hematological Malignancies • Leukemia • Oncology • LIFR • STAT1

Antiproliferative activity of EC359, an inhibitor of leukemia inhibitory factor receptor (LIF-R), singly and in combination with chemotherapy drugs against pancreatic cancer cell lines (AACR 2022) - "Although combination chemotherapy treatments such as FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan), gem-abraxane (gemcitabine and nab-paclitaxel) and GTX (gemcitabine, docetaxel and capecitabine) have improved survival of pancreatic cancer patients incrementally, 5-year-survival for this disease remains dismal...EC359 was also synergistic with IBR120 (a novel small molecule inhibitor of RAD51) against PANC-1 cells...The nanomolar activity of EC359 against pancreatic cancer cell lines makes it a good candidate for potential treatment of this generally refractory disease. The synergistic interaction of EC359 with standard-of-care drugs provides an opportunity for increasing the therapeutic index for these agents, and ultimately improving clinical outcomes for pancreatic cancer and other cancers against which EC359 is currently in clinical trial."

Combination therapy • Preclinical • Breast Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Pancreatic Cancer • Solid Tumor • LIFR • RAD51

LIFR inhibition enhances the therapeutic efficacy of HDAC inhibitors in triple negative breast cancer. (PubMed, Commun Biol) - "Here, we show that first-in-class Leukemia Inhibitory Factor Receptor (LIFRα) inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC...Importantly, combination therapy potently inhibited the growth of TNBC patient derived explants, cell derived xenografts and patient-derived xenografts in vivo. Collectively, our results suggest that targeted inhibition of LIFR can enhance the therapeutic efficacy of HDACi in TNBC."

Clinical • Journal • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • LIFR

Leukemia inhibitory factor receptor inhibition reduces obesity driven progression of triple negative breast cancer (SABCS 2021) - "Treatment of TNBC cells with adipose conditions or HG increased the proliferation and invasion of TNBC cells. Western blot and RT-qPCR analyses confirmed that increased expression of LIFR correlated with enhanced downstream LIFR signaling such as STAT3 and subsequent activation of STAT3 target genes. CRISPR KO of LIFR or treatment of TNBC cells with EC359 significantly reduced the cell viability, colony formation and invasion under adipose conditions."

Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • LIFR • STAT3

LIF/LIFR oncogenic signaling is a novel therapeutic target in endometrial cancer. (PubMed, Cell Death Discov) - "Importantly, EC359 treatment resulted in a significant reduction of the growth of EC patient-derived explants ex vivo, EC cell line-derived xenografts, and patient-derived xenografts in vivo. Collectively, our work revealed the oncogenic potential of the LIF/LIFR axis in EC and support the utility of LIFR inhibitor, EC359, as a novel targeted therapy for EC via the inhibition of LIF/LIFR oncogenic signaling."

Journal • Endometrial Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • LIFR • NANOG • POU5F1 • SOX2

[VIRTUAL] Therapeutic targeting of endometrial cancer with novel LIFR inhibitor EC359 (AACR 2021) - "Collectively, these data support EC359 as a novel targeted therapy for EC by inhibiting LIF/LIFR oncogenic signaling pathway."

Endometrial Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • LIFR