Screening method
This invention relates to a novel screening method that identifies simple molecular markers that are predictive of whether a particular disease condition is responsive to a specific treatment. Also, a method of diagnosing the susceptibility of an individual suffering from a disease to treatment with an HDAC inhibitor is provided. Also provided is a method of treating a proliferative disease or a condition which involves a change in cell differentiation or growth rate in a patient.
1. A method of diagnosing the susceptibility of an individual suffering from cancer to treatment with an HDAC inhibitor, the method comprising assessing the level of expression or activity of a gene's expression product in a sample from a patient and comparing said level of expression or activity to a reference, wherein a level of expression or activity that is different to said reference is indicative of an altered susceptibility to treatment with the HDAC inhibitor relative to the reference state, wherein said gene is Myd88 (myeloid differentiation primary response gene 88), wherein the expression product is a protein, and wherein the protein is detected by an antibody that binds specifically to the Myd88 protein, and wherein the sample comprises tumor cells.
2. The method of claim 1 , wherein a level that is significantly higher than the reference level indicates that the individual is more susceptible to treatment with an HDAC inhibitor, and wherein if a significantly higher level is detected then the method further comprises referring the patient for treatment with the HDAC inhibitor.
3. The method of claim 1 , wherein a level that is significantly lower than the reference level is indicative of an individual's potential resistance to treatment with the HDAC inhibitor.
4. The method of claim 1 , wherein the Myd88 gene is a nucleic acid molecule, which:
(a) comprises a Myd88 sequence recited in accession number NM 002468; or
(b) is a fragment of a sequence according to (a).
5. The method of claim 1 , wherein the expression product is a protein, which:
(a) has an amino acid sequence encoded by a nucleic acid sequence of claim 4 (a); or
(b) is a fragment of a protein according to (a), provided that said fragment retains a biological activity possessed by the full length polypeptide of (a) of acting as an adaptor molecule involved in Toll receptor family signaling, or has an antigenic determinant in common with the polypeptide of (a).
6. The method of claim 1 , wherein the method of diagnosis is facilitated by an array comprising at least two different types of antibody species, wherein each antibody species is immunospecific with a Myd88 protein.
7. The method of claim 1 , wherein said sample is a tissue sample.
8. The method of claim 7 , wherein said sample is blood, urine, saliva, or a specific tissue biopsy.
9. A method of diagnosing the susceptibility of an individual suffering from cancer to treatment with an HDAC inhibitor, the method comprising assessing the level of expression or activity of a gene or its expression products, or the sequence of a gene, in a sample from a patient and comparing said level of expression or activity or sequence to a reference, wherein a level of expression or activity or sequence that is different to said reference is indicative of an altered susceptibility to treatment with the HDAC inhibitor relative to the reference state, wherein said gene is Myd88 (myeloid differentiation primary response gene 88), and wherein the disease is cancer, and wherein the sample comprises tumor cells.
10. A method of diagnosing the susceptibility of an individual suffering from cancer to treatment with an HDAC inhibitor, the method comprising assessing the level of expression or activity of a gene or its expression products, or the sequence of a gene, in a sample from a patient and comparing said level of expression or activity or sequence to a reference,
wherein a level of expression or activity or sequence that is different to said reference is indicative of an altered susceptibility to treatment with the HDAC inhibitor relative to the reference state, and wherein said gene is Myd88 (myeloid differentiation primary response gene 88),
wherein a level that is significantly higher than the reference level indicates that the individual is more susceptible to treatment with an HDAC inhibitor, and
wherein if a significantly higher level is detected then the method further comprises treating said patient with an HDAC inhibitor, and wherein the sample comprises tumor cells.