International journal of molecular sciences, 2020-06, Vol.21 (12), p.4507
2020
Details
- Autor(en) / Beteiligte
- Titel
- The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling
- Ist Teil von
- International journal of molecular sciences, 2020-06, Vol.21 (12), p.4507
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- Oncogenic activation of the phosphatidylinositol-3-kinase (PI3K), protein kinase B (PKB/AKT), and mammalian target of rapamycin (mTOR) pathway is a frequent event in prostate cancer that facilitates tumor formation, disease progression and therapeutic resistance. Recent discoveries indicate that the complex crosstalk between the PI3K-AKT-mTOR pathway and multiple interacting cell signaling cascades can further promote prostate cancer progression and influence the sensitivity of prostate cancer cells to PI3K-AKT-mTOR-targeted therapies being explored in the clinic, as well as standard treatment approaches such as androgen-deprivation therapy (ADT). However, the full extent of the PI3K-AKT-mTOR signaling network during prostate tumorigenesis, invasive progression and disease recurrence remains to be determined. In this review, we outline the emerging diversity of the genetic alterations that lead to activated PI3K-AKT-mTOR signaling in prostate cancer, and discuss new mechanistic insights into the interplay between the PI3K-AKT-mTOR pathway and several key interacting oncogenic signaling cascades that can cooperate to facilitate prostate cancer growth and drug-resistance, specifically the androgen receptor (AR), mitogen-activated protein kinase (MAPK), and WNT signaling cascades. Ultimately, deepening our understanding of the broader PI3K-AKT-mTOR signaling network is crucial to aid patient stratification for PI3K-AKT-mTOR pathway-directed therapies, and to discover new therapeutic approaches for prostate cancer that improve patient outcome.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms21124507Titel-ID: cdi_doaj_primary_oai_doaj_org_article_a980eacb31324e33bfab82ff939ebdfb
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT, AKT protein, Androgen Antagonists - therapeutic use, Androgen receptors, Androgens, Autophagy, Biomarkers, Breast cancer, Cancer therapies, Cascades, castration-resistant prostate cancer (CRPC), Cell cycle, Cell growth, Cell Line, Tumor, Cell Proliferation, Crosstalk, Datasets, Deprivation, Disease resistance, Drug resistance, Gene amplification, Gene expression, Genetic diversity, Growth factors, Humans, Insulin, Invasiveness, Kinases, Male, MAP kinase, MAPK, Medical prognosis, Metastasis, Mitogen-Activated Protein Kinases - metabolism, mTOR, Mutation, Neoplasm Recurrence, Local - genetics, Oncogenes, Phosphatidylinositol 3-Kinase - metabolism, Phosphatidylinositol 3-Kinases - metabolism, Phosphoinositide-3 Kinase Inhibitors - metabolism, Phosphorylation, PI3K, Prostate cancer, Prostatic Neoplasms - genetics, Prostatic Neoplasms - metabolism, Proteins, Proto-Oncogene Proteins c-akt - metabolism, Rapamycin, Receptors, Androgen - metabolism, Review, Signal transduction, Signaling, Testes, TOR protein, TOR Serine-Threonine Kinases - metabolism, Tumorigenesis, Wnt protein, Wnt Signaling Pathway - physiology