Abstract: The present invention relates to the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject. Accordingly, in certain non-limiting embodiments, the present invention provides for methods, compositions and kits for a companion diagnostic for CDK4 inhibitors, and in particular, for the use of the colocalization of Enigma and CDH18 biomarkers to foci within the cancer for determining whether the cancer can be successfully treated by CDK4 inhibition.

Abstract: The present invention relates to the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject. It is based, at least in part, on the discovery that cancer treatment with a CDK4 inhibitor is more effective where treated cancer cells undergo cellular senescence rather than a transient cell cycle arrest, where cellular senescence is associated with decreased MDM2 protein level. Accordingly, in non-limiting embodiments, the present invention provides for methods, compositions, and kits for a companion diagnostic for CDK4 inhibitors, and in particular, to the use of MDM2 expression as a biomarker for the likelihood that a cancer can be successfully treated by CDK4 inhibition.

Abstract: The present invention relates to the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject. It is based, at least in part, on the discovery that cancer cells expressing ATRX prior to treatment are more likely to undergo cellular senescence in response to treatment with a CDK4 inhibitor. It is also based, at least in part, on the discovery that ATRX is phosphorylated in cancer cells that are not as responsive to CDK4 inhibitor therapy. Accordingly, in non-limiting embodiments, the present invention provides for methods, compositions, and kits for a companion diagnostic for CDK4 inhibitors, and in particular, to the use of ATRX expression as a biomarker for determining the likelihood that a cancer can be successfully and/or unsuccessfully treated by CDK4 inhibition.

Abstract: The present invention provides assays for identifying drug candidates that regulate cellular senescence. In particular, the present invention relates to the use of ATRX foci as a biomarker for determining whether one or more drug candidates regulate senescence in a cell line. In one non-limiting embodiment, the present invention provides assays to identify compounds that can be used in a combinatorial cancer treatment. The present invention is based, at least in part, on the discovery that the number of ATRX foci increases in cells that undergo senescence. Accordingly, in non-limiting embodiments, the present invention provides for assays and kits for identifying drug combinations that may be useful in treating subject that have cancer and for identifying compounds that may be useful in treating age-related diseases.

Abstract: The present invention relates to the use of one or more biomarkers to evaluate the likelihood that a CDK4 inhibitor would produce an anti-cancer effect in a subject. It is based, at least in part, on the discovery that cancer treatment with a CDK4 inhibitor is more effective where treated cancer cells undergo cellular senescence rather than a transient cell cycle arrest, where cellular senescence is associated with decreased MDM2 protein level. Accordingly, in non-limiting embodiments, the present invention provides for methods, compositions, and kits for a companion diagnostic for CDK4 inhibitors, and in particular, to the use of MDM2 expression as a biomarker for the likelihood that a cancer can be successfully treated by CDK4 inhibition.