Agents and methods for determining colorectal cancer status
The invention provides a method of determining the colorectal cancer status of subject, comprising applying to a colon and/or rectal surface an agent which is able to distinguish between a) mature glycosylated forms of MUC2 and b) incomplete or aberrant glycosylated forms of MUC2, and determining the extent to which the agent binds.
1. A method of determining the colorectal cancer status of a subject, comprising applying to the subject's colon and/or rectal surface an agent which binds to the mature glycosylated form of Mucin 2 (MUC2) such that it is able to distinguish between a) mature glycosylated forms of MUC2 and b) incomplete or aberrant glycosylated forms of MUC2, and determining the extent to which the agent binds, wherein the agent comprises a lectin or an antibody, and binding of the agent to the mature glycosylated form of MUC2 to colon and/or rectal tissue indicates normal, non-cancerous tissue and the absence of binding to the colon and/or rectal tissue indicates cancer tissue.
2. A method of treating colorectal cancer or dysplasia in a subject comprising:
i) topically applying to the colon and/or rectal region of the subject a labeled agent capable of binding predominantly to either mature glycosylated forms of MUC2 associated with healthy tissue or to incomplete or aberrant glycosylated forms of MUC2 associated with dysplasia or cancer, wherein the agent comprises a lectin or an antibody;
ii) visualizing the colorectal region to which the agent was applied and observing where the agent has bound; and
iii) excising or treating tissue associated with the incomplete or aberrant glycosylated forms of MUC2.
3. The method of claim 2 , wherein the agent is a lectin.
4. The method of claim 3 , wherein the lectin is Wisteria floribunda agglutinin (WFA) or Dolichos biflorus agglutinin (DBA).
5. The method claim 1 , wherein the agent is labeled.
6. A method of determining the colorectal cancer status of the colorectal region of a subject, comprising topically applying to the region a lectin and determining the extent to which it binds.
7. The method of claim 6 , wherein the lectin is selected from WFA and DBA.
8. The method of claim 6 , wherein the lectin binds predominantly to mature glycosylated MUC2 associated with normal tissue.
9. The method of claim 1 , where colorectal cancer status includes one or more of: the presence or absence of colorectal cancer or colorectal dysplasia; the progression of colorectal cancer or colorectal dysplasia; the effectiveness or response of a subject to a treatment for colorectal cancer or colorectal dysplasia; and the prognosis for a subject with colorectal cancer or colorectal dysplasia.
10. The method of claim 1 , wherein the agent is applied to a resected or biopsy sample of colorectal tissue ex vivo or to the colon or rectal surface of a subject in vivo.
11. The method of claim 1 , wherein the agent binds predominantly to mature glycosylated MUC2 associated with normal tissue.
12. An agent which is able to distinguish between (a) mature glycosylated forms of MUC2 and (b) incomplete or aberrant glycosylated forms of MUC2, wherein the agent comprises a lectin or an antibody formulated for topical administration in a carrier comprising one or more of a thickener, lubricant and non-toxic nonionic surfactant.
13. A kit for identifying cancerous or dysplastic colorectal tissue, or for determining colorectal cancer status, in a subject comprising:
i) a labeled agent comprising a lectin or an antibody which binds predominantly to either mature glycosylated forms of MUC2 or to incomplete or aberrant glycosylated forms of MUC2;
ii) instructions to apply the labeled agent topically to the surface of the colon and/or rectal region of a subject, and
iii) a carrier comprising one or more of a thickener, lubricant and/or a non-toxic nonionic surfactant.