Methods for drug discovery

An assay for identifying drug candidates for use in a combinatorial cancer drug treatment, comprising:

• (a) treating one or more non-responsive cells with a first drug candidate;
• (b) treating the one or more first drug candidate-treated cells with a second drug candidate;
• (c) determining the number of ATRX foci per cell in the one or more cells treated with the first and second drug candidates;
• and
• (d) comparing the number of ATRX foci in the one or more cells treated with the first and second drug candidates to a reference,
• where an increase in the number of ATRX foci per cell in the first and second compound-treated cells compared to the reference is indicative that the combination of the first drug and the second drug is likely to be useful as a combinatorial cancer drug therapy.

An assay for identifying drug candidates for use in treating an age-related disease, comprising:

• (a) treating one or more cells with a compound that induces senescence;
• (b) treating the one or more cells with a drug candidate;
• and
• (c) determining the number of ATRX foci per cell in the compound and drug candidate-treated cells, as compared to a reference, where a decrease in the number of ATRX foci per cell or the absence of an increase in the number of ATRX foci per cell compared to the reference is indicative that the drug candidate is likely to be useful as a therapy for treating an age-related disease.

An assay for identifying drug candidates for use in treating an age-related disease, comprising:

• (a) treating one or more cells with a CDK4 inhibitor, where the cells enter a quiescent state upon treatment with the compound that induces senescence.
• (b) treating the one or more CDK4-inhibitor treated cells with shMDM2;
• (c) treating the one or more cells with a drug candidate;
• and
• (d) determining the number of ATRX foci per cell in the CDK4 inhibitor, shMDM2 and drug candidate-treated cells, as compared to a reference, where a decrease in the number of ATRX foci per cell or the absence of an increase in the number of ATRX foci per cell compared to the reference is indicative that the drug candidate is likely to be useful as a therapy for treating age-related disease.