Predicting cancer relapse and treatment of cancer diseases

A method of estimating a likelihood of cancer relapse for a subject following cancer treatment, the method comprising the steps of:

• introducing ex vivo a nucleic acid molecule comprising a reporter gene under transcriptional control of a SOX9 promoter or of a promoter operatively linked to an enhancer element comprising at least one SOX9 binding site into cancer cells obtained from a tumor sample from a subject;
• exposing ex vivo the cancer cells to a cancer treatment;
• determining the amount of SOX9 positive cancer cells following cancer treatment based on expression of the reporter gene;
• and
• estimating a likelihood of cancer relapse following cancer treatment for the subject based on the determined amount of SOX9 positive cancer cells.

An in vitro method of predicting a response to a cancer treatment, the method comprising the steps of:

• introducing (ex vivo i) a nucleic acid molecule comprising a reporter gene under transcriptional control of a SOX9 promoter or of a promoter operatively linked to an enhancer element comprising at least one SOX9 binding site and a suicidal gene under transcriptional control of a SOX9 promoter or of a promoter operatively linked to an enhancer element comprising at least one SOX9 binding site or ii) a first nucleic acid molecule comprising the reporter gene under transcriptional control of a SOX9 promoter or of a promoter operatively linked to an enhancer element comprising at least one SOX9 binding site and a second nucleic acid molecule comprising the suicidal gene under transcriptional control of a SOX9 promoter or of a promoter operatively linked to an enhancer element comprising at least one SOX9 binding site into cancer cells obtained from a tumor sample from a subject, the suicidal gene encodes a prodrug activating protein capable of converting a prodrug or a metabolite thereof into a cytotoxic agent;
• exposing ex vivo the cancer cells to a cancer treatment;
• determining a first amount of SOX9 positive cancer cells following cancer treatment based on expression of the reporter gene;
• adding ex vivo the prodrug to the cancer cells;
• determining a second amount of SOX9 positive cancer cells following addition of the prodrug based on expression of the reporter gene;
• and
• predicting a response of the subject to a cancer treatment based on the determined first and second amounts.