PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a review on drug discovery and future challenges

Khan, Mohammad Ahmed; Jain, Vineet; Rizwanullah, Md.; Ahmad, Javed; Jain, Keerti

doi:10.1016/j.drudis.2019.09.001

Cited by 188 publications

(128 citation statements)

References 61 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…mTORC1 is a downstream molecule of AKT and is activated by phosphorylated AKT. As a PDK2, mTORC2 fully activates AKT by phosphorylating Ser473 [58]. The AKT/ TSC1-TSC2 signalling pathway can also regulate mTOR activity as well as cell growth and proliferation.…”

Section: Akt Target Proteinsmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

469

263

View full text Add to dashboard Cite

The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

show abstract

Section: Akt Target Proteinsmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

469

263

View full text Add to dashboard Cite

show abstract

“…Aberrations in PI3K/AKT/mTOR signaling are common in TNBC and some have suggested this pathway as a therapeutic target ( 124 ). Signaling through PI3K/AKT/mTOR influences several cellular processes including proliferation, invasion, survival, metabolism, and chemoresistance and has been shown to play a role in the initiation and progression of mammary tumorigenesis ( 124 , 127 , 128 ). The above example of multiple compounds in the MD inhibiting the PI3K/AKT/mTOR pathway highlights a significant benefit of using a MD-based approach to aid in TNBC prevention and therapy.…”

Section: Discussionmentioning

confidence: 99%

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

et al. 2020

View full text Add to dashboard Cite

Breast cancer is the most common malignancy and cause of cancer-related mortality among women worldwide. Triple negative breast cancers (TNBC) are the most aggressive and lethal of the breast cancer molecular subtypes, due in part to a poor understanding of TNBC etiology and lack of targeted therapeutics. Despite advances in the clinical management of TNBC, optimal treatment regimens remain elusive. Thus, identifying interventional approaches that suppress the initiation and progression of TNBC, while minimizing side effects, would be of great interest. Studies have documented an inverse relationship between the incidence of hormone receptor negative breast cancer and adherence to a Mediterranean Diet, particularly higher consumption of fish and olive oil. Here, we performed a review of studies over the last 5 years investigating the effects of fish oil, olive oil and their components in model systems of TNBC. We included studies that focused on the fish oil ω-3 essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in addition to olive oil polyphenolic compounds and oleic acid. Both beneficial and deleterious effects on TNBC model systems are reviewed and we highlight how multiple components of these Mediterranean Diet oils target signaling pathways known to be aberrant in TNBC including PI3K/Akt/mTOR, NF-κB/COX2 and Wnt/β-catenin.

show abstract

“…Moreover, TNBC, which is described by deficiency of ER, PR, and HER-2, is associated with the worst prognosis due to increased rates of recurrence and a lack of effective targeted therapies among all major subtypes of BC [17]. Recently, large scale genetic sequencing research has identified many mutations related to the occurrence and development of BC, and gradually outlined the interaction network of breast cancer oncogenes [18][19].…”

Section: Verteporfin Induces Cell Apoptosis By Disrupting Yap-tead Comentioning

confidence: 99%

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Different Subtypes of Breast Cancer Cell Lines Without Light Activation

Wei

2020

Preprint

View full text Add to dashboard Cite

Background Breast cancer (BC) can be separated into four molecular subclassifications including Lumina1 A, Lumina1 B, HER-2 overexpression and Basal-like subtype. These classifications are based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and cell proliferation antigen (Ki-67). The Hippo signaling pathway plays an indispensable role in BC. The YAP1 gene is a terminal effector of Hippo pathway, and hyperactivation of YAP mediates tumorigenesis. As an inhibitor of YAP, non-photoactivated verteporfin (VP) can inhibit YAP-mediated tumor proliferation and angiogenesis by eliminating its interaction with TEAD. This study set out to determine the effect and molecular mechanisms of VP-mediated inhibition of YAP in different subtypes of BC. Methods Luminal A, Luminal B and Basal-like BC cells were cultivated in vitro in order to study effect of VP on proliferation and apoptosis on these three molecular BC subtypes. Results Our experimental results show that VP inhibits cell proliferation, YAP-TEAD interaction and its downstream target expression. VP also induces tumor cell apoptosis, and promotes the cleavage of Caspase-9 and PARP in various molecular subtypes of BC cells. Conclusion These findings provide a basis for VP as a potential anti-tumor therapeutic for BC by targeting the Hippo pathway effector YAP.

show abstract

PI3K/AKT/mTOR pathway inhibitors in triple-negative breast cancer: a review on drug discovery and future challenges

Cited by 188 publications

References 61 publications

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

Verteporfin Inhibits Cell Proliferation and Induces Apoptosis in Different Subtypes of Breast Cancer Cell Lines Without Light Activation

Contact Info

Product

Resources

About