Abstract
Simple SummaryApproximately 2,261,419 new cases of breast cancer (BC) and 684,996 BC-related deaths are estimated to occur in 2020 globally. New individualized therapeutic strategies are urgently needed for affected patients. The aim of our review was to assess the potential role of targeted PDK1 therapies in BC. We hope the information provided on clinical trials of PDK1-targeted therapies will benefit researchers and clinicians in the breast cancer field.Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize the interaction networks of PDK1. Then, we establish the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More importantly, we sort the current preclinical or clinical trials of PDK1-targeted therapy in BC and find that, even though no selective PDK1 inhibitor is currently available for BC therapy, the combination trials of PDK1-targeted therapy and other agents have provided some benefit. Thus, there is increasing anticipation that PDK1-targeted therapy will have its space in future therapeutic approaches related to BC, and we hope the novel approaches of targeted therapy will be conducive to ameliorating the dismal prognosis of BC patients.
Highlights
Introduction published maps and institutional affilAn estimated 19,292,789 new cancer cases and 9,958,133 cancer-related deaths occurred in 2020 worldwide, increasing the global cancer burden
TP53-mutant breast cancer (BC) (69% of tumors were basal-like BCs, BLBCs); they illustrated the molecular heterogeneity of triple negative breast cancer (TNBC) and correlated the relevance of TP53-mutant TNBC to a pretty poor survival. These results suggested a need to classify the subjects in clinical trials [92]
Despite numerous attempts having been made in BC therapy with candidate phosphoinositide-dependent kinase 1 (PDK1) tool compounds, definitive evidence about whether specific inhibitors of PDK1 as monotherapy could achieve favorable results is still lacking; this obliges us to take actions to determine the vulnerabilities of the therapeutic potential in specific PDK1 inhibitors
Summary
Introduction published maps and institutional affilAn estimated 19,292,789 new cancer cases and 9,958,133 cancer-related deaths occurred in 2020 worldwide, increasing the global cancer burden. Of the total new cases, BC) took the place of lung cancer (11.4%, LC) for the first time and became the most frequently occurring cancer worldwide. It ranked the fifth among causes for human cancer-related death globally in 2020 (684,996 deaths, 6.9%) (https://gco.iarc.fr/, accessed on 1 September 2021). In China, BC ranked fourth (416,371 new cases, 9.1%) in the top 10 most frequently occurring cancers and seventh in cancer-related deaths (117,174 deaths, 3.9%), respectively, in this globally recognized list in. In the 2019 World Health Organization (WHO) Classification of Breast Tumors, BC constitutes a series of heterogeneous groups of tumors with marked variations in clinical presentation, biological behavior, and response to therapy [1]. With the development and progression of molecular assays, the classification and management of BC are based iations
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