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Targeting CAMKK2 for the treatment of advanced prostate cancer

Award Number: F31CA310040
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Targeting CAMKK2 for the treatment of advanced prostate cancer - Project Summary Prostate cancer is the second leading cause of cancer-related deaths in men. While localized prostate cancer can be cured with surgery and androgen deprivation therapy (ADT), metastatic, castration-resistant prostate cancer (CRPC) remains incurable and resistant to current therapies. One major challenge in treating CRPC is its cold, immunosuppressive tumor microenvironment, which leads to poor response to immune checkpoint therapies. Given the success of immunotherapy in other cancers, finding ways to sensitize prostate cancer to immunotherapy is critical. Calcium/calmodulin-dependent kinase kinase 2 (CAMKK2) is a downstream target of the androgen receptor (AR), which regulates CRPC progression by promoting cancer cell growth and proliferation. CAMKK2 expression is linked to CRPC progression, and studies have shown that it enhances prostate cancer cell migration and invasion, indicating a cancer cell-intrinsic role in metastasis. Previous work in the Frigo lab demonstrated a potential cancer cell-extrinsic role for CAMKK2, where CAMKK2 knockout mice exhibited impaired tumor growth when injected with wild-type CRPC cells. In other cancers, CAMKK2 has been shown to regulate the immune tumor microenvironment, particularly by influencing myeloid cells. CAMKK2 ablation has been linked to increased immune infiltration into tumors, but this has not been investigated in prostate cancer. Since the immunosuppressive prostate cancer tumor microenvironment limits the effectiveness of immunotherapy, understanding the role of CAMKK2 in the immune tumor microenvironment could provide new therapeutic options to patients. The most widely used CAMKK2 inhibitor, STO-609, lacks specificity and targets other kinases with similar affinity. This project will assess the efficacy of newly developed CAMKK2 inhibitors and degraders, evaluating their impact on prostate cancer metastasis and the immune microenvironment in preclinical models of advanced CRPC compared to STO-609. Aim 1 of this project will investigate the cancer cell-intrinsic and -extrinsic mechanisms of CAMKK2 in regulating CRPC metastasis and the immune tumor microenvironment of CRPC. Aim 2 will evaluate the efficacy of novel CAMKK2 targeting agents in impairing prostate cancer progression and in influencing immune infiltration into tumors. Completion of these aims will establish CAMKK2 as a promising therapeutic target for advanced prostate cancer and provide a foundation for future clinical trials. Under the mentorship of Drs. Frigo, Karacosta, and Goswami, I will gain expertise in preclinical mouse models, single-cell omics, and expand my knowledge of cancer immunology. During this fellowship, I aim to present my research at conferences and advisory meetings, publish 1-2 first-author papers, and develop skills for a successful career as an independent cancer researcher leading my own laboratory studying metabolic signaling pathways, mechanisms of metastasis, and therapy resistance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Research Manpower	001	1	8/11/2026	NEW	$0
2026	2026	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Research Manpower	000	1	8/11/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Targeting CAMKK2 for the treatment of advanced prostate cancer

Award Number: F31CA310040

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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