ONCase (recombinant methionine α, γ-lyase) / AntiCancer, Shionogi, Nantong Jinghua - LARVOL DELTA

Selective Synergy of the Combination of Recombinant Methioninase With Cisplatinum and Ivermectin Which Eradicates Lung-Cancer Cells but Has No Synergy and Limited Effect on Normal Fibroblasts. (PubMed, Anticancer Res) - "The present study demonstrated that the combination of rMETase, cisplatinum, and ivermectin exerts selective synergy on lung-cancer cells, which was not observed on normal fibroblasts. Moreover, the present combination therapy has a strong synergistic efficacy at early time points on the lung-cancer cells. Further studies are warranted to elucidate the underlying mechanisms of synergy of the present combination treatment selectively on cancer cells and to evaluate the in vivo efficacy and safety of the present treatment strategy."

Journal • Breast Cancer • CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Psychiatry • Solid Tumor

The Combination of Recombinant Methioninase and Low-dose Chloroquine Selectively Eradicates Colon-Cancer Cells Without Apparent Toxicity on Co-cultured Normal Fibroblasts. (PubMed, Anticancer Res) - "rMETase has selective efficacy against cancer cells in the presence of normal cells, and its efficacy is significantly enhanced selectively on the cancer cells by CQ. The results of the present study suggest the potential for future clinical application of the combination of rMETase and CQ for cancer treatment."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

Rapid Eradication of Extensive Spinal Metastases in a Prostate-Cancer Patient Taking Androgen-deprivation Therapy, Chemotherapy, and Oral Recombinant Methioninase on a Low-Methionine Diet. (PubMed, Anticancer Res) - "The patient achieved an apparent complete response of prostate-cancer spinal metastases after treatment with ADT, chemotherapy, and methionine restriction. Further studies, including controlled clinical trials are necessary to validate this new paradigm of treatment for prostate-cancer bone metastases."

Clinical • Journal • CNS Disorders • Genito-urinary Cancer • Oncology • Prostate Cancer • Psychiatry • Solid Tumor

Very Rapid Eradication of a Large Squamous-Cell Carcinoma of the Head and Neck Treated With First-line Combination Chemotherapy, a Low-methionine Diet, and Oral Recombinant Methioninase. (PubMed, Anticancer Res) - "The combination of first-line chemotherapy, a low-methionine diet, and o-rMETase rapidly eradicated a very large HNSCC. The present results suggest this combination should be further tested, including clinical trials, as the regimen is highly effective in the present case and can possibly avoid disfiguring surgery and harmful radiation."

Journal • CNS Disorders • Head and Neck Cancer • Oncology • Psychiatry • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Triple Combination of Recombinant Methioninase and the Anti-parasitic Drugs Ivermectin, and Chloroquine Selectively Eradicates Pancreatic Cancer Cells While Sparing Normal Fibroblasts. (PubMed, Anticancer Res) - "The combination of rMETase, ivermectin, and chloroquine exhibited a selective cytotoxic synergy against pancreatic-cancer cells while sparing normal fibroblasts. Furthermore, the order of treatment may also affect efficacy. This triple combination treatment may offer a novel and effective first-line therapeutic approach for pancreatic cancer."

Journal • CNS Disorders • Oncology • Pancreatic Cancer • Psychiatry • Solid Tumor

Simultaneous Targeting of Multiple Hallmarks of Cancer With Recombinant Methioninase, Rapamycin and Chloroquine Is Specific and Synergistic to MiaPaCa-2 Pancreatic-Cancer Cells in Contrast to Hs-27 Normal Fibroblasts. (PubMed, Anticancer Res) - "The combination of rMETase, rapamycin and chloroquine had highly synergistic and selective efficacy against PDAC cells in vitro compared to normal cells, supporting its potential as a precision-targeted metabolic clinical therapy for pancreatic cancer."

Journal • CNS Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Psychiatry • Solid Tumor

Recombinant Methioninase Selectively Eliminates Cancer Cells Co-cultured With Normal Fibroblasts Indicating the High-Precision Efficacy of Targeting Methionine Addiction of Cancer. (PubMed, Anticancer Res) - "The differential sensitivity of cancer and normal cells to rMETase at 0.46 U/ml was so extensive that cancer cells were essentially eliminated from the co-cultures while the normal cells remained viable and proliferating. The difference in sensitivity of normal and cancer cells growing together suggests that rMETase selectively and precisely targets methionine addiction of cancer and can be a safe and effective clinical anti-cancer agent."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

Eradication of Extensive Lymph-Node, Bone and Pleural Metastases of a Breast-Cancer Patient Treated With Radiation, Immunotherapy and Oral Recombinant Methioninase. (PubMed, Cancer Diagn Progn) - "The patient was immediately started on systemic drug therapy with tamoxifen and leuprorelin, but it failed to suppress the tumor...o-rMETase in combination with immunotherapy and irradiation eradicated extensive metastases in a patient with breast cancer. Further investigation of this combination treatment for breast cancer is necessary including clinical trials."

Journal • Breast Cancer • CNS Disorders • Oncology • Psychiatry • Solid Tumor

Combinations of Salmonella typhimurium A1-R, Recombinant Methioninase, and Chloroquine, Each Targeting Fundamental Cancer Hallmarks, Are Selectively Effective on Colon Cancer Cells Compared to Normal Fibroblasts. (PubMed, Anticancer Res) - "Tumor-targeting with A1-R combined with methionine restriction (rMETase) or autophagy inhibition (CQ) resulted in selective and synergistic cytotoxicity against colon-cancer cells compared to normal fibroblasts. The present findings support the clinical potential of the combination of A1-R, rMETase, and CQ for recalcitrant colon cancer."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

The Triple Combination of Recombinant Methioninase, Rapamycin, and Chloroquine Synergistically Eradicates HCT116 Colon Cancer Cells. (PubMed, Anticancer Res) - "The triple combination of rMETase, RAPA and CQ shows strong synergistic efficacy on the human HCT116 colon cancer cell line. The results of the present study suggest the potential for future clinical applications of this triple-combination treatment for advanced/metastatic colon cancer."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

The Conditions of Non-rescuability of Methioninase-treated Cancer Cells by Methionine Replenishment: The Point of No Return. (PubMed, Anticancer Res) - "Three distinct responses to methionine replenishment following rMETase treatment were observed in HCT-116 cells. First, complete recovery and resumption of proliferation occurred with low-dose rMETase at all time points and with short-term treatment at intermediate doses of r-METase. Second, prolonged intermediate-dose treatment or short-term high-dose treatment, resulted in continued proliferation arrest without further cell death. Third, high-dose rMETase treatment for six days led to cell death."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

The Combination of the Autophagy Inhibitor Chloroquine and Recombinant Methioninase Has Selective Synergistic Efficacy on Human Colon Cancer Cells But Not on Normal Human Fibroblasts. (PubMed, Anticancer Res) - "The combination of chloroquine and rMETase had synergistic efficacy on colon-cancer cells, but not on normal fibroblasts. rMETase is used clinically as an oral supplement, and chloroquine is a drug approved for clinical use. Therefore, the combination of rMETase and chloroquine has the potential for safe clinical application."

Journal • Breast Cancer • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Osteosarcoma • Psychiatry • Sarcoma • Solid Tumor

Selective Synergy of Ivermectin Combined With Recombinant Methioninase Against Colon-Cancer Cells in Contrast to Normal Fibroblasts. (PubMed, Anticancer Res) - "rMETase and ivermectin showed selective synergistic anti-cancer efficacy against colon-cancer cells, indicating the clinical potential of the combination for metastatic CRC."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor

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

Recombinant Methioninase and Cisplatinum Act Synergistically to Inhibit Lewis Lung Carcinoma Cells But Not Normal Fibroblasts. (PubMed, Anticancer Res) - "Combination therapy with rMETase and CDDP shows promise for treating lung cancer and may be readily translated to the clinic."

Journal • CNS Disorders • Lung Cancer • Oncology • Psychiatry • Solid Tumor

Efficacy of Methionine Restriction and the PARP-inhibitor Olaparib and Their Combination on BRCA1 Mutant and Wild-type Triple-negative Breast Cancer Cell Lines. (PubMed, Anticancer Res) - "Methionine restriction and olaparib showed synergistic efficacy on the BRCA1-mutant TNBC cell line HCC1937. The BRCA1-mutant cell line MDA-MB-436 was most sensitive to rMETase. The BRCA1/2 wild-type TNBC cell line MDA-MB-231 was sensitive to a methionine-free medium but resistant to olaparib. Therefore, methionine restriction has clinical potential for BRCA1/2 wild-type and BRCA1-mutant olaparib-resistant and -sensitive TNBC."

Journal • Preclinical • Breast Cancer • CNS Disorders • Oncology • Psychiatry • Solid Tumor • Triple Negative Breast Cancer • BRCA1 • BRCA2

Super Methotrexate-resistant Osteosarcoma Cells Retain Their Sensitivity to Recombinant Methioninase: Targeting Methionine Addiction to Overcome Extreme Cancer-Chemotherapy Resistance. (PubMed, Anticancer Res) - "rMETase overcame a 5,500-fold MTX-resistance of osteosarcoma cells. The present results suggest methionine restriction by rMETase can be a potential clinical strategy to overcome recalcitrant drug-resistance in osteosarcoma."

Journal • CNS Disorders • Oncology • Osteosarcoma • Psychiatry • Sarcoma • Solid Tumor • DHFR

Highly Synergistic Eradication of 143B Osteosarcoma Cells In Vitro by the Combination of Recombinant Methioninase, Chloroquine, and Rapamycin Targeting Methionine Addiction, Autophagy, and mTOR, Respectively. (PubMed, Anticancer Res) - "The triple combination of rMETase, CQ, and RAPA demonstrated strong synergy and effectively eradicated 143B osteosarcoma cells. Therefore, the triple treatment with rMETase, CQ, and RAPA has potential as a novel, effective therapeutic approach for osteosarcoma."

Journal • Preclinical • CNS Disorders • Oncology • Osteosarcoma • Psychiatry • Sarcoma • Solid Tumor

Engineered Methioninase-expressing Tumor-targeting Salmonella typhimurium A1-R Inhibits Syngeneic-Cancer Mouse Models by Depleting Tumor Methionine. (PubMed, Cancer Genomics Proteomics) - "Tumor-targeting Salmonella typhimurium A1-R engineered to express the Pseudomonas putida methioninase gene, inhibited LLC tumor growth in a syngeneic mouse model and reduced the methionine level in the tumor. Salmonella typhimurium A1-R-rMETase combines the tumor targeting and killing capability of Salmonella typhimurium A1-R plus rMETase which targets the methionine addiction of cancer."

Journal • Preclinical • CNS Disorders • Lung Cancer • Oncology • Psychiatry • Solid Tumor

Targeting Methionine Addiction of Osteosarcoma with Methionine Restriction to Overcome Drug Resistance: A New Paradigm for a Recalcitrant Disease. (PubMed, Cancers (Basel)) - "First-line chemotherapy for osteosarcoma, including methotrexate (MTX), doxorubicin (DOX), and cisplatinum (CDDP), targets cells in the S/G2-phase, where cancer cells are also inhibited by methionine restriction, resulting in the synergy of methionine restriction to overcome drug resistance. In the present review, we describe the synergistic efficacy of conventional chemotherapy and methionine restriction therapy, including rMETase, in overcoming the drug resistance of osteosarcoma. The clinical potential of this new paradigm to overcome the drug resistance of osteosarcoma is discussed."

Journal • CNS Disorders • Oncology • Osteosarcoma • Psychiatry • Sarcoma • Solid Tumor

Recombinant Methioninase (rMETase) Synergistically Sensitizes Ivermectin-resistant MCF-7 Breast Cancer Cells 9.9 Fold to Low-dose Ivermectin. (PubMed, Anticancer Res) - "The combination of ivermectin and rMETase had synergistic efficacy against MCF-7 breast cancer cells in vitro. The present findings suggest that the combination of ivermectin and rMETase is a promising strategy for breast cancer requiring further preclinical and clinical evaluation."

Journal • Breast Cancer • CNS Disorders • Oncology • Psychiatry • Solid Tumor

Selective Synergy of Recombinant Methioninase Plus Docetaxel Against Docetaxel-resistant and -sensitive Fibrosarcoma Cells Compared to Normal Fibroblasts. (PubMed, Anticancer Res) - "The combination of docetaxel and rMETase was synergistic on HT1080 fibrosarcoma cells, but not normal fibroblasts. rMETase plus docetaxel synergistically reduced the high docetaxel resistance of DTR-HT1080 cells. The present results indicate the clinical potential of rMETase to reduce docetaxel resistance in soft-tissue sarcoma patients in the future."

Journal • CNS Disorders • Fibrosarcoma • Oncology • Psychiatry • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Recombinant Methioninase Synergistically Reverses High-docetaxel Resistance Developed in Osteosarcoma Cells. (PubMed, Anticancer Res) - "rMETase reversed docetaxel resistance of DTR-143B in vitro. The present results indicate the clinical potential of rMETase to overcome docetaxel resistance in osteosarcoma patients."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Extensive DNA Damage and Loss of Cell Viability Occur Synergistically With the Combination of Recombinant Methioninase and Paclitaxel on Pancreatic Cancer Cells which Report DNA-Damage Response in Real Time. (PubMed, Cancer Genomics Proteomics) - "The present study suggests the synergy of methionine restriction and chemotherapy is due, at least in part, to DNA damage of cancer cells."

Journal • CNS Disorders • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Psychiatry • Solid Tumor • TP53BP1

First-line Chemotherapy in Combination With Oral Recombinant Methioninase and a Low-methionine Diet for a Stage IV Inoperable Pancreatic-Cancer Patient Resulted in 40% Tumor Reduction and an 86% CA19-9 Biomarker Decrease. (PubMed, Anticancer Res) - "Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer."

Biomarker • Combination therapy • Journal • Metastases • CNS Disorders • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Psychiatry • Solid Tumor • CA 19-9