Efficacy of Recombinant Methioninase on Late-stage Patient Cancer in the Histoculture Drug Response Assay (HDRA) as a Potential Functional Biomarker of Sensitivity to Methionine-restriction Therapy in the Clinic.

BACKGROUND/AIM: The present study utilized the three-dimensional histoculture drug response assay (HDRA) to determine the efficacy of recombinant methioninase (rMETase) on tumor tissue resected from patients with late-stage cancer, as a functional biomarker of sensitivity to methionine restriction therapy.

PATIENTS AND

METHODS

Resected peritoneal-metastatic cancer, including colorectal cancer, pancreatic cancer, ovarian cancer, and pseudomyxoma were placed on Gelform in RPMI 1640 medium for seven days and treated with rMETase from 2.5 U/ml to 20 U/ml. Cell viability was determined using the MTT assay. A total of 48 patients with late-stage cancer underwent testing for rMETase responsiveness using the HDRA.

RESULTS

Colorectal cancer and pseudomyxoma had the highest sensitivity to rMETase. Pancreatic and ovarian cancer also responded to rMETase, but to a lesser degree.

CONCLUSION

Patients with tumors with at least 40% sensitivity to rMETase in the HDRA are being considered as candidates for methionine restriction therapy, which includes the use of rMETase in combination with a low-methionine diet.