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New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventio...

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Published in:Pathology, research and practice research and practice, 2023-11, Vol.251, p.154902-154902, Article 154902
Main Authors: Sadrkhanloo, Mehrdokht, Paskeh, Mahshid Deldar Abad, Hashemi, Mehrdad, Raesi, Rasoul, Bahonar, Alireza, Nakhaee, Zahra, Entezari, Maliheh, Beig Goharrizi, Mohammad Ali Sheikh, Salimimoghadam, Shokooh, Ren, Jun, Nabavi, Noushin, Rashidi, Mohsen, Dehkhoda, Farshid, Taheriazam, Afshin, Tan, Shing Cheng, Hushmandi, Kiavash
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container_title Pathology, research and practice
container_volume 251
creator Sadrkhanloo, Mehrdokht
Paskeh, Mahshid Deldar Abad
Hashemi, Mehrdad
Raesi, Rasoul
Bahonar, Alireza
Nakhaee, Zahra
Entezari, Maliheh
Beig Goharrizi, Mohammad Ali Sheikh
Salimimoghadam, Shokooh
Ren, Jun
Nabavi, Noushin
Rashidi, Mohsen
Dehkhoda, Farshid
Taheriazam, Afshin
Tan, Shing Cheng
Hushmandi, Kiavash
description Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance. [Display omitted]
doi_str_mv 10.1016/j.prp.2023.154902
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The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance. 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Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance. 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subjects gene therapy
non-coding RNAs
Osteosarcoma
PI3K/Akt
PTEN
Resistant
title New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis
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