[Methionine dependency of cancer cells: a new therapeutic approach?].
Metabolic abnormalities of tumor cells offer opportunities of therapeutic targeting. In contrast to normal cells, tumor cells have absolute requirement for methionine (Met), an essential amino acid. Many molecular mechanisms have been considered to explain Met dependency. Several approaches have been used To reduce Met in vivo. As the main Met source was food, synthetic Met free diet were widely used. Alternatively, Met restriction was archived by the use of Met analogs or enzymatic degradation by methioninase. In animal models, Met restriction permit to limit tumor growth and to reduce tumor volume. However, interruption of Met restriction induce the regrowth of tumor. Moreover Met restriction induce several cells modifications suggesting its use in association with conventional chemotherapy. Preclinical studies have shown synergistic effect of the association of Met restriction and different cytostatic agents. Currently, few clinical investigations have been realised to test this therapeutic strategy.
Durando
Xavier
X
Département d'oncologie médicale, Centre Jean Perrin, 58, rue Montalembert, 63011 Clermont-Ferrand, France.
Thivat
Emilie
E
Gimbergues
Pierre
P
Cellarier
Eric
E
Abrial
Catherine
C
Dib
Mathilde
M
Tacca
Olivier
O
Chollet
Philippe
P
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D013437:Carbon-Sulfur Lyases / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008715:Methionine / Q000008:administration & dosage* / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D008715:Methionine; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase; D005472:Fluorouracil