Treatment of hippo pathway mutant tumors and methods of identifying subjects as candidates for treatment
The present invention relates to a method of treating a tumor in a subject. This method involves administering to a subject having a Hippo pathway mutant tumor a tankyrase inhibitor, where the tumor is susceptible to treatment with the tankyrase inhibitor, and said administering is carried out to treat the tumor. The present invention also relates to a method of treating cancer in a subject, and a method of identifying a subject as a candidate for treatment.
1. A method of treating a tumor comprising a Hippo pathway mutant in a subject, said method comprising:
administering to a subject identified as having a Hippo pathway mutant tumor a tankyrase inhibitor, wherein the tumor is susceptible to treatment with the tankyrase inhibitor; wherein the tankyrase inhibitor increases the level of an angiomotin protein family member present in cells of the tumor by at least 4-fold, as compared to when the tankyrase inhibitor is not administered; wherein the increased level of the angiomotin protein family member is sustained for at least 6 days after said administering; and wherein said administering is carried out to treat the tumor in the subject.
2. The method according to claim 1 , wherein the tumor comprises mutations in one or more Hippo pathway genes selected from the group consisting of LATS1, LATS2, NF2, and YAP.
3. The method according to claim 1 , wherein the tankyrase inhibitor is a small molecule.
4. The method according to claim 3 , wherein the tankyrase inhibitor is selected from XAV939, MN-64, IWRI, a pyrimidinone nicotinamide mimetic, and combinations thereof.
5. The method according to claim 1 wherein the angiomotin protein family member is selected from the group consisting of AMOT, AMOTL1, and AMOTL2.
6. The method according to claim 1 , wherein the subject is a human.
7. The method according to claim 1 further comprising:
identifying a subject with a tumor susceptible to treatment with the tankyrase inhibitor prior to said administering.
8. The method according to claim 7 , wherein said identifying comprises:
obtaining a tissue sample from a tumor in the subject and
determining whether the tissue sample from the tumor exhibits a Hippo pathway mutation and if so, the level and durability of angiomotin stabilization in the tissue sample from the tumor following treatment with the tankyrase inhibitor.
9. A method of treating cancer associated with a tumor comprising a Hippo pathway mutant in a subject, said method comprising:
administering a tankyrase inhibitor to a subject identified as having a cancer comprising a Hippo pathway mutant tumor susceptible to treatment with a tankyrase inhibitor, wherein the tankyrase inhibitor increases the level of an angiomotin protein family member present in cells of the tumor by at least 4-fold, as compared to when the tankyrase inhibitor is not administered; wherein the increased level of the angiomotin protein family member is sustained for at least 6 days after said administering; and wherein the tankyrase inhibitor treats the subject for cancer.
10. The method according to claim 9 , wherein the tumor comprises a mutation in one or more Hippo pathway genes selected from the group consisting of LATS1, LATS2, NF2, and YAP.
11. The method according to claim 9 , wherein the tankyrase inhibitor is a small molecule.
12. The method according to claim 9 , wherein the tankyrase inhibitor is selected from XAV939, MN-64, IWRI, a pyrimidinone nicotinamide mimetic, and combinations thereof.
13. The method according to claim 9 , wherein the angiomotin protein family member is selected from the group consisting of AMOT, AMOTL1, and AMOTL2.
14. The method according to claim 9 , wherein the subject is a human.