Abstract: Ovarian cancer, a common gynecologic malignancy, is associated with a poor prognosis owing to difficulties in early detection, high recurrence rates, and frequent therapy resistance. Salt-inducible kinase 2 (SIK2), a serine/threonine kinase frequently overexpressed in ovarian cancer, has emerged as a potential key driver of tumor progression. It is implicated in diverse processes, including metabolic reprogramming, cell proliferation, DNA damage repair, metastasis, and chemoresistance. Consequently, SIK2 is increasingly recognized as a promising target for developing novel therapeutic strategies. Unlike previous reviews that broadly cover the SIK family or general ovarian cancer metabolism, this review provides a SIK2-centered perspective, comprehensively synthesizing its multifaceted oncogenic roles and systematically evaluating emerging targeted therapies—including ATP-competitive inhibitors (ARN-3261, MRIA9), a protein degrader (SIC-19), and a novel hydrogel delivery system (Gel Nap-S+HG). Despite these promising developments, it is important to note that most SIK2-targeted agents are still in preclinical stages, and several critical hurdles remain to be addressed before clinical translation—including off-target toxicity, limited selectivity, and the lack of validated predictive biomarkers for patient stratification. By integrating current mechanistic insights with an up-to-date evaluation of emerging therapies, this review provides a foundational framework for guiding future research and supporting the clinical development of SIK2-targeted strategies in ovarian cancer. Keywords: salt-inducible kinase 2, ovarian cancer, molecular mechanisms, targeted therapy, kinase inhibitors
Xu et al. (Sun,) studied this question.