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Mini-Review: PDPK1 (3-phosphoinositide dependent protein kinase-1), An Emerging Cancer Stem Cell Target
Bogdan Domrachev1, Sitanshu Singh1, Dandan Li2
1Rare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Abstract:
Cancer stem cells (CSCs) are subpopulations of tumor cells that possess abilities for self-renewal, differentiation, and tumor initiation. These rare but therapy-recalcitrant cells are assumed to repopulate tumors following administration of systemic chemotherapy driving therapy failure, tumor recurrence, and disease progression. In early clinical trials, anti-CSC therapies have found limited success to-date possibly due to the inherent heterogeneity and plasticity of CSCs and the incomplete characterization of essential CSC targets. Here, we review the role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as an emerging CSC target. While most previous studies have relied on CSC models which are based on lineage and tissue-specific marker profiles to define the relationships between putative target and CSC traits, this review discusses PDPK1 and its role in CSC biology with an emphasis on CSC systems which are based on proposed function like label-retaining cancer cells (LRCCs).
Insights
Cancer stem cells (CSCs) drive tumor recurrence and treatment failure. This review highlights 3-phosphoinositide dependent protein kinase-1 (PDPK1) as a potential therapeutic target for overcoming CSC resistance.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Cancer stem cells (CSCs) are crucial for tumor initiation, recurrence, and resistance to therapy.
- Current anti-CSC therapies show limited success due to CSC heterogeneity and plasticity.
- Identifying novel CSC targets is essential for improving cancer treatment outcomes.
Purpose of the Study:
- To review the emerging role of 3-phosphoinositide dependent protein kinase-1 (PDPK1) as a therapeutic target in cancer stem cells.
- To discuss PDPK1's function in CSC biology, particularly in label-retaining cancer cells (LRCCs).
Main Methods:
- Literature review focusing on studies investigating PDPK1 in CSCs.
- Analysis of CSC models, including those based on functional characteristics like LRCCs.
- Synthesis of current knowledge on PDPK1's involvement in CSC self-renewal, differentiation, and therapy resistance.
Main Results:
- PDPK1 is implicated in critical CSC functions, suggesting its potential as a therapeutic target.
- Previous research often defined CSCs by markers, but functional definitions (e.g., LRCCs) offer new insights into targets like PDPK1.
- Emerging evidence supports PDPK1's role in CSC-driven tumor progression and treatment failure.
Conclusions:
- PDPK1 represents a promising target for developing novel anti-cancer therapies aimed at eliminating CSCs.
- Further research focusing on functional CSC models is needed to fully elucidate PDPK1's role and therapeutic potential.
- Targeting PDPK1 may offer a strategy to overcome chemotherapy resistance and prevent tumor recurrence driven by CSCs.
