Role and progress of arginine and its rate-limiting enzyme in the treatment of colorectal cancer

Abstract

The treatment for colorectal cancer presents a major challenge worldwide, ranking second to lung cancer in terms of
yearly fatalities. Early detection and surgery are the mainstays of current treatment; additionally, adjuvant anticancer
agents are imperative. There is controversy surrounding the use of arginine in treating colorectal cancer, with two
main approaches: arginine deprivation and arginine supplementation. Arginine is essential for the development and
progression of colorectal cancer. As a result, arginine deprivation therapy suggests that pegylated arginine deaminase
(ADI-PEG) and pegylated human recombinant Arg-1 (rhArg1-PEG) supplements should be taken in the absence of
argininosuccinate synthetase-1 (ASS1) and argininosuccinate lyase (ASL). This would further reduce the supply of
exogenous arginine, which can effectively inhibit tumor development. Nevertheless, studies have revealed that low
L-arginine levels in tumors restrict T cell activation and proliferation, which, in turn, reduces the immune response and
negatively impacts tumor therapy—furthermore, colonizing MC38 tumors with ECN that produce.
High levels of L-Arg combined with anti-PD-L1 antibody significantly improved the effectiveness of PD-L1-mediated
immunotherapy. This paper reviews arginine’s theoretical and preclinical findings and its rate-limiting enzyme-related
adjuvant therapy for colorectal cancer.