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

Synergy of KRAS-inhibitor Daraxonrasib Combined With Recombinant Methioninase on Pancreatic-cancer Cells But Not Normal Cells. (PubMed, Anticancer Res) - "The present results suggest that the combination of daraxonrasib and rMETase has clinical potential for lowering the effective dose of daraxonrasib, thereby reducing daraxonrasib-associated side-effects, as well as increasing its efficacy."

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

The Phosphatidylinositol 3-Kinase (PI3K) Inhibitor Inavolisib Has Breast-cancer Synergy Combined With Recombinant Methioninase But Not on Normal Cells. (PubMed, In Vivo) - "IVB had a very low IC50 on MCF-7 breast-cancer cells compared to Hs-27 normal fibroblasts. IVB had increased efficacy on MCF-7 breast-cancer cells when combined with rMETase, showing strong synergy. In contrast, the combination of rMETase and IVB showed no synergy on Hs-27 normal fibroblasts. Therefore, IVB in combination with rMETase has strong clinical potential for breast cancer and possibly other cancers."

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

Direct comparison of efficacy of combining ivermectin versus five first-line chemotherapy drugs with recombinant methioninase against colon-cancer cells. (PubMed, Front Oncol) - "At the IC50 concentration, ivermectin combined with rMETase (CI, 6.7 ± 1.9) was significantly (p < 0.05) more effective than rMETase combined with 5-fluorouracil (CI, 2.0 ± 0.7); cisplatinum (CI, 2.4 ± 1.5); gemcitabine (CI, 2.5 ± 0.7); and paclitaxel (CI, 2.8 ± 0.5). Only doxorubicin combined with rMETase was slightly more effective than rMETase combined with ivermectin (CI, 7.8 ± 1.7). Ivermectin combined with rMETase was more effective than four of five first-line chemotherapy drugs combined with rMETase against colon-cancer cells, demonstrating additional promise of ivermectin as an anticancer drug."

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

Chemotherapy in Combination With Methionine Restriction Induced A Complete Response in a Patient With Recurrent Metastatic Tongue Squamous-Cell Carcinoma. (PubMed, Cancer Diagn Progn) - "Following further progression, combination chemotherapy with paclitaxel and cetuximab was administered in combination with methionine restriction (MR), consisting of a low-methionine diet and oral recombinant methioninase (rMETase), rMETase was produced using recombinant Escherichia coli expressing the methioninase gene from Pseudomonas putida and purified by standard methods...MR may represent a promising metabolic therapeutic approach for refractory HNSCC. Αdditional cases and prospective clinical trials are necessary."

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

The Combination of Methionine Adenosyltransferase 2A (MAT2A) Inhibitor AG-270 and Recombinant Methioninase Is Not Cancer-selective in a Co-culture Model of Colon Cancer Cells and Normal Fibroblasts. (PubMed, Cancer Diagn Progn) - "In contrast, rMETase combined with numerous first-line chemotherapeutic drugs acted selectively and synergistically against cancer cells while sparing normal cells, including co-culture models. The present results suggest that AG-270 may have limited potential as an anticancer agent."

Journal • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor • MAT2A

Sulfasalazine an Inhibitor of System xC - (Cystine/glutamate Antiporter), Combined With Recombinant Methioninase, Inhibits Both Cancer and Normal Cells, Suggesting Lack of Cancer Selectivity of Cysteine Restriction. (PubMed, Anticancer Res) - "SSZ shows comparable growth inhibition in cancer and normal cells and displays enhanced efficacy in combination with rMETase on both cell types. These findings suggest that cysteine restriction, unlike methionine restriction, is not a cancer-specific vulnerability."

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

Tumor-targeting Salmonella A1-R selectively delivers recombinant methioninase and inhibits syngeneic-cancer mouse models (AACR 2024) - "Tumor-targeting Salmonella A1-R modified to express the Pseudomonas putida methioninase gene (A1-R-rMETase), inhibited LLC tumor growth in a syngeneic mouse model and reduced the methionine level in the tumor. A1-R-rMETase combines the tumor targeting and killing capability of A1-R itself and restriction methionine selectively in tumors."

Preclinical • Lung Cancer • Oncology • Solid Tumor • CD8

M1-like macrophage infiltration, CD8+ T cell activation, and increased cancer cell apoptosis in immunologically cold Lewis lung carcinoma treated with tumor-trophic Salmonella Typhimurium expressing anticancer proteins in immunocompetent C57BL/6 mice (AACR 2024) - "These findings indicate that VNP20009_rMETase_TNFα anticancer bacteria can disrupt the tumor microenvironment in the cold LLC tumors and active innate and adaptive anti-cancer immune responses in immunocompetent mice. Further, we are investigating additional cold solid mouse tumor models to validate our findings and how this can apply to bacteria-based immunotherapy."

IO biomarker • Preclinical • Hematological Malignancies • Lung Cancer • Oncology • Solid Tumor • CD8 • TNFA

Thirty Years of Mentoring by "Bob Chan" of Young Japanese Surgeons to Become Scientists: An Adventure of Love. (PubMed, Ann Gastroenterol Surg) - "Many of our mentees now lead research laboratories and academic departments across Japan, continuing the cycle of innovation and global partnership. We reflect on this journey as a successful model for training surgeon-scientists and advancing precision cancer therapy through visualization, imagination, and mentorship."

Journal • Review • CNS Disorders • Oncology • Psychiatry • Solid Tumor

Ultra-low Concentrations of Cisplatinum Down to the IC10 in Combination With Recombinant Methioninase Are Synergistically Effective Against Lung Cancer Cells In Vitro and In Vivo. (PubMed, In Vivo) - "Methionine restriction enhances the efficacy of ultra-low-dose cisplatinum on lung cancer cells in vitro. Low-dose cisplatinum in combination with an MR diet prevented lung-cancer growth in nude mice. The present approach of cancer therapy may help reduce platinum-related toxicity and improve treatment outcomes, suggesting further investigation for clinical translation."

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

Lack of Cancer Specificity of Methionine Adenosyltransferase 2A (MAT2A) Inhibitor AG-270 in Combination With Recombinant Methioninase In Vitro. (PubMed, Anticancer Res) - "AG-270 showed lack of cancer specificity in combination with rMETase when tested on both cancer and normal cells. The present results contrast with numerous chemotherapy agents, which in combination with rMETase are synergistic on cancer cells but not on normal cells. The present findings suggest that MAT2A inhibition affects crucial metabolic pathways in normal as well as cancer cell types and thus AG-270 may not be suitable as a cancer-specific therapeutic strategy."

Journal • Preclinical • CNS Disorders • Colon Cancer • Colorectal Cancer • Oncology • Psychiatry • Solid Tumor • MAT2A

Methionine Restriction Must Be Continuously Maintained to Selectively Inhibit Cancer Cells Co-cultured With Normal Cells. (PubMed, Cancer Diagn Progn) - "Continuous treatment with rMETase is necessary to maintain inhibition of cancer cells and normal-cell dominance in co-culture with cancer cells. These results have clinical implications indicating that methionine restriction must be continually maintained to inhibit cancer."

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

Effect of Recombinant Methioninase Dose and Timing on the Selective and Precise Elimination of Cancer Cells from Co-Cultured Normal Cells and on Methionine-dependent Rescue of Cancer Cells. (PubMed, Anticancer Res) - "The ability of rMETase to eliminate cancer cells co-cultured with normal cells is dose-dependent. Even at high effective doses of rMETase, the cancer cells could be rescued by methionine supplementation up to at least day-6, indicating the need for the continuous presence of rMETase to selectively inhibit the cancer cells."

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

Human fibrosarcoma cells selected for ultra-high doxorubicin resistance, acquire trabectedin cross-resistance, remain sensitive to recombinant methioninase, and have increased c-MYC expression. (PubMed, Front Oncol) - "The findings indicate that rMETase can overcome ultra-high doxorubicin resistance in fibrosarcoma cells, likely through targeting methionine addiction, a universal metabolic vulnerability of cancer. These results support the potential clinical application of methionine restriction therapy to treat doxorubicin-resistant STS."

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

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