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Targeting PI3K/mTOR Signaling in Cancers
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Targeting PI3K/mTOR Signaling in Cancers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 11904

Special Issue Editor

Dr. Premila Leiphrakpam

E-Mail Website
Guest Editor
Division of Surgical Oncology, Department of Surgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
Interests: global cancer research; colorectal cancer; pancreatic cancer; cancer biology; cancer metastasis; cancer biomarkers; molecular biology; cell survival; apoptosis; signaling pathways; medical education
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling cascade is a key regulator of cell growth, survival, metabolism, cell cycle progression, cell motility, and angiogenesis in physiological as well as pathological conditions such as cancer. The PI3K/mTOR signaling pathway is aberrantly activated in many cancers due to activation by the receptor tyrosine kinases and somatic mutations in specific components of the signaling pathway. This aberrant activation is critical in driving tumor initiation, progression, and metastasis, and is one of the main mechanisms of resistance to cancer therapy. The complex nature of the PI3K/mTOR pathway, attributed to multiple levels of feedback and crosstalk with other pathways, could contribute to the difficulty in targeting this pathway in cancers. Therefore, the identification of novel molecules at different levels of the PI3K/mTOR pathway is crucial for understanding the precise mechanism of this pathway and its inhibition.

The goal of this Special Issue is to summarize and enlarge the current knowledge on the molecular aspects of PI3K/mTOR signaling in cancer. Authors are welcome to submit original basic and translational research and review articles.

Dr. Premila Leiphrakpam
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • cell survival
  • apoptosis
  • cell proliferation
  • cell cycle regulation
  • metabolism
  • cytoskeleton rearrangement
  • angiogenesis
  • epithelial-to-mesenchymal transition
  • signaling pathway aberrations
  • signaling crosstalk
  • tumorigenesis
  • tumor cell migration
  • metastasis
  • novel markers
  • anti-cancer agents

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Published Papers (2 papers)

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11 pages, 1613 KiB  
Article
Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
by Helena Codina-Martínez, Sara Lucila Lorenzo-Guerra, Virginia N. Cabal, Rocío García-Marín, Laura Suárez-Fernández, Blanca Vivanco, Paula Sánchez-Fernández, Fernando López, José Luis Llorente and Mario A. Hermsen
Int. J. Mol. Sci. 2023, 24(20), 15110; https://doi.org/10.3390/ijms242015110 - 12 Oct 2023
Cited by 4 | Viewed by 1774
Abstract
Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to [...] Read more.
Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients. Full article
(This article belongs to the Special Issue Targeting PI3K/mTOR Signaling in Cancers)
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Review

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20 pages, 1352 KiB  
Review
PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment
by Premila D. Leiphrakpam and Chandrakanth Are
Int. J. Mol. Sci. 2024, 25(6), 3178; https://doi.org/10.3390/ijms25063178 - 9 Mar 2024
Cited by 49 | Viewed by 9451
Abstract
In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results [...] Read more.
In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results in treatment resistance, underscoring the need to understand the molecular mechanisms involved in CRC for the development of novel targeted therapies. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) signaling pathway axis is a major pathway altered in CRC. The aberrant activation of this pathway is associated with CRC initiation, progression, and metastasis and is critical for the development of drug resistance in CRC. Several drugs target PI3K/Akt/mTOR in clinical trials, alone or in combination, for the treatment of CRC. This review aims to provide an overview of the role of the PI3K/Akt/mTOR signaling pathway axis in driving CRC, existing PI3K/Akt/mTOR-targeted agents against CRC, their limitations, and future trends. Full article
(This article belongs to the Special Issue Targeting PI3K/mTOR Signaling in Cancers)
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