There is currently no cure for castration-resistant prostate cancer (CRPC). Further, standard of care treatments such as hormone therapy have associated comorbidities. Thus, mechanistically new treatment strategies are needed. We previously demonstrated an important role for Ca2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in prostate cancer progression. But new data indicate that our previous understanding of how CAMKK2 promotes prostate cancer was incomplete. The goal of this proposal is to delineate emerging cancer cell-intrinsic and -extrinsic roles for CAMKK2 in advanced prostate cancer. We anticipate that systemic CAMKK2 inhibition may also sensitize tumors to other treatment...

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There is currently no cure for castration-resistant prostate cancer (CRPC). Further, standard of care treatments such as hormone therapy have associated comorbidities. Thus, mechanistically new treatment strategies are needed. We previously demonstrated an important role for Ca2+/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in prostate cancer progression. But new data indicate that our previous understanding of how CAMKK2 promotes prostate cancer was incomplete. The goal of this proposal is to delineate emerging cancer cell-intrinsic and -extrinsic roles for CAMKK2 in advanced prostate cancer. We anticipate that systemic CAMKK2 inhibition may also sensitize tumors to other treatment modalities and hence, will create additional, previously unrecognized therapeutic opportunities. To achieve our goals, we will explore new roles for CAMKK2 in prostate cancer metabolism and the immune system. We predict that our mechanistic studies will identify novel ways to treat prostate cancer and nominate potential companion biomarkers. Given CAMKK2's diverse roles in prostate cancer combined with data indicating that systemic inhibition of CAMKK2 is safe, we also anticipate that CAMKK2 inhibitors could be readily combined with existing therapies to enhance their effects and possibly even off-set known side effects. We predict that the research proposed here will provide the impetus for new drug discovery efforts focused on the development of a clinical-grade CAMKK2 inhibitor.

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