REVIEW: Targeting Methionine Addiction of Cancer Cells with Methioninase

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Vadim S. Pokrovsky^1,2,3,a*, Louay Abo Qoura^1,2,b, Elena A. Demidova¹, Qinghong Han⁴, and Robert M. Hoffman^4,5,c

¹Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, 115478 Moscow, Russia

²Research Institute of Molecular and Cellular Medicine, People’s Friendship University of Russia (RUDN University), 117198 Moscow, Russia

³Department of Biotechnology, Sirius University of Science and Technology, 354340 Sochi, Russia

⁴AntiCancer Inc., San Diego, CA 92111 USA

⁵Department of Surgery, University of California, San Diego, La Jolla, CA 92037-7400 USA

^* To whom correspondence should be addressed.

Received February 11, 2023; Revised March 12, 2023; Accepted March 13, 2023

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All types of cancer cells are addicted to methionine, which is known as the Hoffman effect. Restricting methionine inhibits the growth and proliferation of all tested types of cancer cells, leaving normal cells unaffected. Targeting methionine addiction with methioninase (METase), either alone or in combination with common cancer chemotherapy drugs, has been shown as an effective and safe therapy in various types of cancer cells and animal cancer models. About six years ago, recombinant METase (rMETase) was found to be able to be taken orally as a supplement, resulting in anecdotal positive results in patients with advanced cancer. Currently, there are 8 published clinical studies on METase, including two from the 1990s and six more recent ones. This review focuses on the results of clinical studies on METase-mediated methionine restriction, in particular, on the dosage of oral rMETase taken alone as a supplement or in combination with common chemotherapeutic agents in patients with advanced cancer.

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KEY WORDS: methionine addiction, Hoffman effect, methionine γ-lyase, methionine-degrading enzyme, oral methioninase, clinical study, methionine restriction

DOI: 10.1134/S0006297923070076

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