The lab led by Everardo Macias, PhD, has been awarded a three-year Department of Defense (DOD) grant for over $1 million for fiscal year 2022. The lab’s research, titled “Targeting NUAK2 in Neuroendocrine Prostate Cancer,” was accepted as part of the DOD Prostate Cancer Research Program (PCRP) Idea Development Award-Established Investigator PC220197 program. The objective of the Lab’s proposal is to test the potential of NUAK Family Kinase 2 (NUAK2) as a therapeutic target for neuroendocrine prostate cancer.
Neuroendocrine prostate cancer is lethal and aggressive, and commonly develops as a resistance mechanism in heavily treated, late-stage metastatic castrate resistant prostate cancer. This is referred to as treatment-emergent neuroendocrine prostate cancer, and approximately 20-25% of late-stage prostate cancer patients develop it. Neuroendocrine prostate cancer patients often present with high metastatic burden and the prognosis is poor, with a five-year survival rate of less than 20%. So, there is an urgent need for new actionable molecular targets to combat neuroendocrine prostate cancer.
The Macias Lab recently published that NUAK2 is a highly actionable protein that can be exploited as a target for prostate cancer therapy and they used investigational NUAK2 inhibitor to slow the growth of prostate cancer in mice with no observable toxicities. In new unpublished studies, they found that NAUK2 expression progressively increases as prostate cancer advances. In patient-derived preclinical models, the expression of NUAK2 was most elevated in neuroendocrine prostate cancer subtypes. Their preliminary experiments show that genetic or pharmacological targeting of NUAK2 in neuroendocrine prostate cancer cells slowed their growth rate.
Next, they plan to test NUAK2 inhibitor compound in the more advanced and lethal neuroendocrine prostate cancer subtype. They have also identified FDA-approved compounds which bind NUAK2 very potently and slow neuroendocrine prostate cancer cell growth in preliminary studies. They propose to exploit these FDA-approved drugs for their beneficial NUAK2 off-target activity. If successful, progression to clinical applications should occur quickly, benefitting patients diagnosed with lethal neuroendocrine prostate cancer.