Marker for determination of sensitivity to anti-cancer agent

Patent metadata

Field	Value
Publication number	US-8945929-B2
Application number	US-86572509-A
Country	US
Kind code	B2
Filing date	Jan 30, 2009
Priority date	Jan 31, 2008
Publication date	Feb 3, 2015
Grant date	Feb 3, 2015

Abstract

Provided are a marker for determining sensitivity to an anticancer agent capable of distinguishing a therapeutic response of an individual patient and a novel means for a cancer therapy using the marker. The marker for determining sensitivity to an anticancer agent contains a substance in a metabolic pathway in which L-phenylalanine and/or N,N-dimethyl glycine are/is involved.

First claim

The invention claimed is:

1. A method of determining sensitivity of colorectal cancer to an anticancer agent, comprising
(a) obtaining a biological sample from a subject having colorectal cancer;
(b) measuring a concentration of at least one marker selected from the group consisting of L-phenylalanine and N,N-dimethyl glycine in said biological sample obtained in (a);
(c) administering to said subject an anticancer agent selected from the group consisting of irinotecan, a salt of irinotecan, SN-38, and a salt of SN-38;
(d) obtaining a biological sample from said subject following said administering;
(e) measuring a concentration of at least one marker selected from the group consisting of L-phenylalanine and N,N-dimethyl glycine in said biological sample obtained in (d);
(f) comparing the concentration of said at least one marker measured in (e) to the concentration of said at least one marker measured in (b) to determine whether said colorectal cancer is sensitive to said anticancer agent.

2. The method according to claim 1 , wherein said marker is L-phenylalanine.

3. The method according to claim 1 , wherein the anticancer agent is irinotecan or a salt thereof.

4. The method according to claim 1 , wherein the anticancer agent is SN-38 or a salt thereof.

5. The method according to claim 1 , wherein in (f)
when the concentration of said at least one marker in (e) is greater than the concentration of said at least one marker in (b), the colorectal cancer is not sensitive to said anticancer agent;
when the concentration of said at least one marker in (e) is the same as than the concentration of said at least one marker in (b), the colorectal cancer is not sensitive to said anticancer agent; and
when the concentration of said at least one marker in (e) is less than the concentration of said at least one marker in (b), the colorectal cancer is sensitive to said anticancer agent.

6. The method according to claim 1 , wherein said marker is N,N-dimethyl glycine.

7. A method of determining whether an anticancer drug would provide a therapeutic response in a subject having colorectal cancer, comprising
(a) obtaining a biological sample from a subject having colorectal cancer;
(b) measuring a concentration of at least one marker selected from the group consisting of L-phenylalanine and N,N-dimethyl glycine in said biological sample obtained in (a);
(c) administering to said subject an anticancer agent selected from the group consisting of irinotecan, a salt of irinotecan, SN-38, and a salt of SN-38;
(d) obtaining a biological sample from said subject following said administering;
(e) measuring a concentration of at least one marker selected from the group consisting of L-phenylalanine and N,N-dimethyl glycine in said biological sample obtained in (d);
(f) comparing the concentration of said at least one marker measured in (e) to the concentration of said at least one marker measured in (b) to determine whether said anticancer agent would provide a therapeutic response in said subject.

8. The method according to claim 7 , wherein said marker is L-phenylalanine.

9. The method according to claim 7 , wherein the anticancer agent is irinotecan or a salt thereof.

10. The method according to claim 7 , wherein the anticancer agent is SN-38 or a salt thereof.

11. The method according to claim 7 , wherein in (f)
when the concentration of said at least one marker in (e) is greater than the concentration of said at least one marker in (b), the anticancer agent does not provide a therapeutic effect;
when the concentration of said at least one marker in (e) is the same as than the concentration of said at least one marker in (b), the anticancer agent does not provide a therapeutic effect; and
when the concentration of said at least one marker in (e) is less than the concentration of said at least one marker in (b), the anticancer agent provides a therapeutic effect.

12. The method according to claim 7 , wherein said marker is N,N-dimethyl glycine.

Assignees

• Tanigawara Yusuke
• Watanabe Mitsuhiro
• Arita Eri
• Nishimuta Akito
• Yamayoshi Yasuko
• Matsuzaki Takeshi
• Sugimoto Shinji
• Univ Keio
• Yakult Honsha Kk

Inventors

• Tanigawara Yusuke
• Watanabe Mitsuhiro
• Arita Eri
• Nishimuta Akito
• Yamayoshi Yasuko
• Matsuzaki Takeshi
• Sugimoto Shinji

Classifications

• G01N33/6812

  Assays for specific amino acids · CPC title

• Y10S436/813

  Cancer · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title

• A61K31/4745 Primary

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title