The elevated
methionine (MET) requirement of
cancer cells is termed MET dependence and is possibly the only known general metabolic defect in
cancer. Targeting MET by recombinant
methioninase (rMETase) can arrest the growth of
cancer cells in vitro and in vivo due to their elevated requirement for MET. rMETase can also potentiate
chemotherapy drugs active in S phase due to the selective arrest of
cancer cells in S/G2 phase during MET restriction (MR). We previously reported that rMETase, administrated by
intraperitoneal injection (ip-rMETase), could inhibit
tumor growth in mouse models of
cancer including patient-derived orthotopic xenograft (PDOX) mouse models. We subsequently compared ip-rMETase and oral rMETase (o-rMETase) on a
melanoma PDOX mouse model. o-rMETase was significantly more effective than ip-rMETase to inhibit
tumor growth without overt toxicity. The combination of o-rMETase+ip-rMETase was significantly more effective than either monotherapy and completely arrested
tumor growth. Thus, o-rMETase is effective as an
anticancer agent with the potential of clinical development for chronic
cancer therapy as well as for
cancer prevention. o-rMETase may also have potential as an antiaging agent for healthy people, since MR has been shown to extend the life span of a variety of different organisms.