PIK3CA Mutation Analysis in Iranian Patients with Gastric Cancer

Iranpour, Mostafa; Nourian, Mahyar; Saffari, Sana; Samizadeh, Esmaeil; Mirghafori, Mahdieh; Iravani, Siavash; Ghafouri‐Fard, Soudeh

doi:10.29252/ibj.23.1.87

Cited by 8 publications

(3 citation statements)

References 15 publications

(24 reference statements)

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“…It is considered that PIK3CA is the second most common mutated gene in GC, responsible for 4-25% of cases, and also found in 85% of EBV GC cases [156]. Iranpour and his research group analyzed 100 patients with GC who underwent surgical resection and detected mutations in exon 20 of the PI3KCA gene in 11% of GC patients [157].…”

Section: Pi3k/akt/mtor and Mapk Pathways In Gastric Cancermentioning

confidence: 99%

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

Morgos,

Stefani,

Miricescu

et al. 2024

IJMS

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Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)—PI3K/AKT/mTOR—and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

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Section: Pi3k/akt/mtor and Mapk Pathways In Gastric Cancermentioning

confidence: 99%

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

Morgos,

Stefani,

Miricescu

et al. 2024

IJMS

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“…In the anti‐proliferative activity of 182 malignant tumor cells, it was observed to inhibit the growth inhibitory activity of 41 malignant tumor cells, especially in breast cancer cells . The growth of human BT474 breast cancer was markedly suppressed in xenograft models following the use of AZD5363 . More recently, AZD5356 has been extensively investigated, alone or in combination, in a considerable number of phase I or II clinical trials.…”

Section: Atp‐competitive Akt Inhibitorsmentioning

confidence: 99%

Recent Advance of Akt Inhibitors in Clinical Trials

et al. 2019

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The serine/threonine kinase Akt, also known as protein kinase B (PKB), exerts a critical role in the phosphoinositide 3-kinase (PI3 K)-Akt signaling pathway that involves in cell growth, proliferation, apoptosis and neo-angiogenesis. Inhibition of Akt results in blockade of cell-cycle progression and growth of tumors. Therefore, focusing on the drug design strategies to develop potent antitumor agents targeting Akt has been hot spot research areas. In this review, we summarized the intracellular functions of Akt, and outlined the development of Akt inhibitors in clinical trials.

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“…The key enzyme in this pathway is PI3K, which regulates the expression of sub-signals by phosphorylating phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol (3,4,5)-trisphosphate (PIP3) [ 15 ]. Moreover, mutations in PI3KCA , a PI3K gene, increase downstream signaling pathways and promote tumor growth in various tumors [ 16 – 19 ]. Therefore, PI3K is considered an important therapeutic target, and research on PI3K inhibitors has been actively conducted over the last decade.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer effect of palmatine through inhibition of the PI3K/AKT pathway in canine mammary gland tumor CMT-U27 cells

Yoo,

Choi,

Jang

et al. 2023

BMC Vet Res

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Canine mammary gland tumors (CMTs) are the most common and lethal cancers in female dogs. Dysregulated phosphoinositide 3-kinases (PI3K)/AKT pathway reportedly was involved in the growth and metastasis of CMTs. However, there are few studies on therapeutic strategies for targeting the PI3K pathway in CMTs. In this study, we aimed to determine whether palmatine, a natural isoquinoline alkaloid with anti-cancer properties, could inhibit the growth of CMTs and whether the inhibitory effect was mediated through the PI3K/AKT pathway. Our in vitro experiments on CMT-U27, a CMT cell line, showed that palmatine reduced cell proliferation and induced cell death. Western blotting results revealed that palmatine decreased the protein expression of PI3K, PTEN, AKT, and mechanistic target of rapamycin in the PI3K/AKT pathway, which was supported by the results of immunocytochemistry. Additionally, palmatine suppressed the migration and tube formation of canine aortic endothelial cells as well as the migration of CMT U27 cells. Our in vivo results showed that palmatine inhibited tumor growth in a CMT-U27 mouse xenograft model. We observed a decreased expression of proteins in the PI3K/AKT pathway in tumor tissues, similar to the in vitro results. Furthermore, palmatine significantly disrupted the tumor vasculature and inhibited metastasis to adjacent lymph nodes. In conclusion, our findings demonstrate that palmatine exerts anti-cancer effects against CMTs by inhibiting PI3K/AKT signaling pathway, suggesting that palmatine has potential as a canine-specific PI3K inhibitor for the treatment of CMTs.

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PIK3CA Mutation Analysis in Iranian Patients with Gastric Cancer

Cited by 8 publications

References 15 publications

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

Recent Advance of Akt Inhibitors in Clinical Trials

Anti-cancer effect of palmatine through inhibition of the PI3K/AKT pathway in canine mammary gland tumor CMT-U27 cells

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