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

Morgos, Diana-Theodora; Stefani, Constantin; Miricescu, Daniela; Greabu, Maria; Stanciu, Silviu; Nica, Silvia; Stanescu-Spinu, Iulia-Ioana; Balan, Daniela Gabriela; Balcangiu-Stroescu, Andra-Elena; Coculescu, Elena-Claudia; Georgescu, Dragos-Eugen; Nica, Remus Iulian

doi:10.3390/ijms25031848

Open AccessReview

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

by

Diana-Theodora Morgos

^1,†,

Constantin Stefani

^2,*,

Daniela Miricescu

^3,*,

Maria Greabu

³,

Silviu Stanciu

^4,†,

Silvia Nica

⁵

,

Iulia-Ioana Stanescu-Spinu

⁶,

Daniela Gabriela Balan

⁶,

Andra-Elena Balcangiu-Stroescu

⁶,

Elena-Claudia Coculescu

⁷,

Dragos-Eugen Georgescu

^8,9

and

Remus Iulian Nica

^10,11

¹

Discipline of Anatomy, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania

²

Department I of Family Medicine and Clinical Base, “Dr. Carol Davila” Central Military Emergency University Hospital, 010825 Bucharest, Romania

³

Discipline of Biochemistry, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania

⁴

Department of Internal Medicine and Gastroenterology, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, 010825 Bucharest, Romania

⁵

Emergency Discipline, University Hospital of Bucharest, 050098 Bucharest, Romania

⁶

Discipline of Physiology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania

⁷

Discipline of Oral Pathology, Faculty of Dentistry, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania

⁸

Department of General Surgery, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 50474 Bucharest, Romania

⁹

Department of General Surgery, “Dr. Ion Cantacuzino” Clinical Hospital, 020475 Bucharest, Romania

¹⁰

Central Military Emergency University Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania

¹¹

Discipline of General Surgery, Faculty of Midwifery and Nursing, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania

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^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2024, 25(3), 1848; https://doi.org/10.3390/ijms25031848

Submission received: 21 December 2023 / Revised: 26 January 2024 / Accepted: 31 January 2024 / Published: 3 February 2024

(This article belongs to the Special Issue Signaling Pathways Dysregulation in Cancer: Advances and New Therapeutics Hopes)

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Abstract

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.

Keywords: gastric cancer; PI3K/AKT/mTOR; MAPK; gene mutations; bacterial infection; dysregulation; inhibitors

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MDPI and ACS Style

Morgos, D.-T.; Stefani, C.; Miricescu, D.; Greabu, M.; Stanciu, S.; Nica, S.; Stanescu-Spinu, I.-I.; Balan, D.G.; Balcangiu-Stroescu, A.-E.; Coculescu, E.-C.; et al. Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. Int. J. Mol. Sci. 2024, 25, 1848. https://doi.org/10.3390/ijms25031848

AMA Style

Morgos D-T, Stefani C, Miricescu D, Greabu M, Stanciu S, Nica S, Stanescu-Spinu I-I, Balan DG, Balcangiu-Stroescu A-E, Coculescu E-C, et al. Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. International Journal of Molecular Sciences. 2024; 25(3):1848. https://doi.org/10.3390/ijms25031848

Chicago/Turabian Style

Morgos, Diana-Theodora, Constantin Stefani, Daniela Miricescu, Maria Greabu, Silviu Stanciu, Silvia Nica, Iulia-Ioana Stanescu-Spinu, Daniela Gabriela Balan, Andra-Elena Balcangiu-Stroescu, Elena-Claudia Coculescu, and et al. 2024. "Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer" International Journal of Molecular Sciences 25, no. 3: 1848. https://doi.org/10.3390/ijms25031848

APA Style

Morgos, D.-T., Stefani, C., Miricescu, D., Greabu, M., Stanciu, S., Nica, S., Stanescu-Spinu, I.-I., Balan, D. G., Balcangiu-Stroescu, A.-E., Coculescu, E.-C., Georgescu, D.-E., & Nica, R. I. (2024). Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. International Journal of Molecular Sciences, 25(3), 1848. https://doi.org/10.3390/ijms25031848

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

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