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Cited by 7Ovarian cancer diagnosis and treatmentNeuroendocrine Tumor Research AdvancesGrowth Hormone and Insulin-like Growth Factors

Duplication of AKT2 Gene in Ovarian Cancer: A Potentially Novel Mechanism for Tumor-Induced Hypoglycemia

Open access
Alkaissi, Hussam R, Mostel, Zachary, McFarlane, Samy I·2022·Cureus
DOI 10.7759/cureus.25813PMC PMC9271230
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Abstract

Severe hypoglycemia occurs with different types of tumors, including islet cell and non-islet cell tumors. Non-islet cell tumor hypoglycemia (NICTH) is a rare and potentially life-threatening complication of malignancy. The primary underlying mechanism of NICTH proposed in the literature includes paraneoplastic overproduction of insulin-like growth factor-2 (IGF-2), the production of autoantibodies against insulin or its receptors, or the presence of extensive metastatic burden replacing hepatic tissue or adrenal glands. In this report, we propose a potentially novel mechanism underlying NICTH involving stimulation of the insulin signaling pathway in a 58-year-old woman with a rare ovarian tumor of Müllerian origin that carries a duplication of the AKT2 gene. AKT2 is a molecular mediator of insulin signaling. To our knowledge, this is the first reported case of tumor-induced hypoglycemia associated with AKT2 gene duplication. In this report also, we discuss the currently available diagnostic modalities and highlight the therapeutic rationale in patients with NICTH, a highly vulnerable population.

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  • Alpelisib and copanlisib are FDA-approved medications for metastatic breast cancer and work by inhibiting phosphoinositide 3-kinase (PI3K).

    “Alpelisib and copanlisib are two FDA-approved medications for metastatic breast cancer and work by inhibiting phosphoinositide 3-kinase (PI3K) [47].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [47]

  • Protease inhibitors used in the treatment of HIV competitively inhibit GLUT4, leading to decreased glucose uptake and transient insulin resistance, both of which may be beneficial to treat NICTH-induced hypoglycemia.

    “Lastly, protease inhibitors used in the treatment of HIV competitively inhibit GLUT4, leading to decreased glucose uptake and transient insulin resistance, both of which may be beneficial to treat NICTH-induced hypoglycemia [47].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [47]

  • Hyperglycemia is a notable side effect of PI3K inhibitors and occurs in up to 63% of patients.

    “Hyperglycemia is a notable side effect and occurs in up to 63% of patients [47].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [47]

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Cited by

Sorted by citations

Authors
Alkaissi, H. R., Mostel, Z., & McFarlane, S. I.
Affiliations
SUNY Downstate Health Sciences University (US)
Corresponding author
Alkaissi, Hussam R
ORCID
Venue
Cureus
Publisher
Springer Science and Business Media LLC
Published
2022-06-10
Volume
14
Issue
6
Pages
e25813-e25813
ISSN
2168-8184 (ISSN-L)
DOI
10.7759/cureus.25813
PMC
PMC9271230
OpenAlex
W4283390773
Cited by
7
References
1
Citations by year
2025: 2 · 2024: 5
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cureus (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
  • Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
tumor-induced hypoglycemia, non-islet cell tumor hypoglycemia, ovarian cancer, Müllerian tumors, insulin signaling pathway, insulin-like growth factor II, insulin receptor antibodies

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