Combination therapy for treating cancer and diagnostic assays for use therein

1. A combination of therapeutic agents for use in treating a patient suffering from cancer, wherein said combination comprises:

a) at least one polyploidy inducing agent for use in inducing polyploidization in one or more cancer cells in the patient; and

b) at least one Bcl-2 family protein inhibitor having the following structure (II):

or a therapeutically acceptable salt thereof; wherein

X 3 is chloro or fluoro; and

(1) X 4 is azepan-1-yl, morpholin-1-yl, 1,4-oxazepan-4-yl, pyrrolidin-1-yl, N(CH 3 ) 2 , N(CH 3 )(CH(CH 3 ) 2 ), 7-azabicyclo[2.2.1]heptan-1-yl or 2-oxa-5-azabicyclo[2.2.1]hept-5-yl; and

R 0 is

wherein X 5 is CH 2 , C(CH 3 ) 2 or CH 2 CH 2 ; X 6 and X 7 are both hydrogen or both methyl; and X 8 is fluoro, chloro, bromo or iodo; or,

(2) X 4 is azepan-1-yl, morpholin-1-yl, pyrrolidin-1-yl, N(CH 3 )(CH(CH 3 ) 2 ), or 7-azabicyclo[2.2.1]heptan-1-yl; and

R 0 is

wherein X 6 and X 7 are both hydrogen or both methyl; and X 8 is fluoro, chloro, bromo or iodo; or,

(3) X 4 is N(CH 3 ) 2 or morpholin-1-yl; and

R 0 is

wherein X 8 is fluoro, chloro, bromo or iodo.

2. The combination of claim 1 , wherein the at least one polyploidy inducing agent is an Aurora Kinase inhibitor.

3. The combination of claim 2 , wherein the Aurora Kinase inhibitor is an Aurora Kinase B inhibitor.

4. The combination of claim 3 , wherein the Aurora Kinase B inhibitor is VX-680 or AZD1152.

5. The combination of claim 1 , wherein the Bcl-2 family protein inhibitor is ABT-263.

6. A method of treating a patient suffering from cancer, the method comprising the steps of:

a) administering to a patient suffering from cancer a therapeutically effective amount of at least one polyploidy inducing agent; and

b) administering to the patient a therapeutically effective amount of at least one Bcl-2 family protein inhibitor having the structure (11) of claim 1 ,

wherein the cancer is a lymphoid malignancy of B-cell origin or a small cell lung cancer.

7. The method of claim 6 , wherein the at least one polyploidy inducing agent is an Aurora Kinase inhibitor.

8. The method of claim 7 , wherein the Aurora Kinase inhibitor is an Aurora Kinase B inhibitor.

9. The method of claim 8 , wherein the Aurora Kinase B inhibitor is VX-680 or AZD1152.

10. The method of claim 6 , wherein the Bcl-2 family protein inhibitor is ABT-263.