Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Wan, Huiying; Zhang, Dingding; Hu, Weimin; Xie, Zhen; Du, Qiu; Xia, Qiongrong; Wen, Taishen; Jia, Haiping

doi:10.1097/md.0000000000026779

Cited by 5 publications

(9 citation statements)

References 43 publications

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“…Corradini et al 114 identified PTEN mutants in 50% in radiotherapy-induced ASs. 114 Studies showed that AS has weak PTEN immunoreactivity, 115 and in high-grade tumours PTEN expression was largely absent. 116 Human and canine tumours share PTEN mutants not only in the case of AS, 115,[117][118][119] but also in mammary tumours and gliomas.…”

Section: Alterations Of Intracellular Signalling Pathways and Importa...mentioning

confidence: 99%

“…114 Studies showed that AS has weak PTEN immunoreactivity, 115 and in high-grade tumours PTEN expression was largely absent. 116 Human and canine tumours share PTEN mutants not only in the case of AS, 115,[117][118][119] but also in mammary tumours and gliomas. 27 Inactivating PTEN mutation in HSA was detected in between 6% and 15% of cases 13 in several independent studies based on exome sequence analyses, mostly together with TP53 mutation.…”

Section: Alterations Of Intracellular Signalling Pathways and Importa...mentioning

confidence: 99%

“…Corradini et al 114 identified PTEN mutants in 50% in radiotherapy‐induced ASs 114 . Studies showed that AS has weak PTEN immunoreactivity, 115 and in high‐grade tumours PTEN expression was largely absent 116 …”

Section: Alterations Of Intracellular Signalling Pathways and Importa...mentioning

confidence: 99%

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New molecular targets in canine hemangiosarcoma—Comparative review and future of the precision medicine

Kapturska

Pawlak

2023

Vet Comparative Oncology

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Human angiosarcoma and canine hemangiosarcoma reveal similarities not only in their aggressive clinical behaviour, but especially in molecular landscape and genetic alterations involved in tumorigenesis and metastasis formation. Currently, no satisfying treatment that allows for achieving long overall survival or even prolonged time to progression does not exist. Due to the progress that has been made in targeted therapies and precision medicine the basis for a new treatment design is to uncover mutations and their functions as possible targets to provide tailored drugs for individual cases. Whole exome or genome sequencing studies and immunohistochemistry brought in the last few years important discoveries and identified the most common mutations with probably crucial role in this tumour development. Also, despite a lack of mutation in some of the culprit genes, the cancerogenesis cause may be buried in main cellular pathways connected with proteins encoded by those genes and involving, for example, pathological angiogenesis. The aim of this review is to highlight the most promising molecular targets for precision oncology treatment from the veterinary perspective aided by the principles of comparative science. Some of the drugs are only undergoing laboratory in vitro studies and others entered the clinic in the management of other cancer types in humans, but those used in dogs with promising responses have been mentioned as priorities.

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Section: Alterations Of Intracellular Signalling Pathways and Importa...mentioning

confidence: 99%

Section: Alterations Of Intracellular Signalling Pathways and Importa...mentioning

confidence: 99%

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New molecular targets in canine hemangiosarcoma—Comparative review and future of the precision medicine

Kapturska

Pawlak

2023

Vet Comparative Oncology

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“…In the quality miRNAseq control, all samples exhibited a phred value ranging from 35 to 40. Phred levels are typically categorised as poor (0-20), medium (20)(21)(22)(23)(24)(25)(26)(27)(28), and good (>28). Therefore, all samples demonstrated high quality.…”

Section: The Subsequent Qpcr Experiments Validated the Consistency Ofmentioning

confidence: 99%

“…10 Recent research has demonstrated that the PTEN pathway is frequently disrupted in canine haemangiosarcoma, either through inactivating mutations or epigenetic downregulation. 3,[11][12][13] MicroRNAs (miRNAs) are small RNA molecules, typically [18][19][20][21][22][23][24][25] nucleotides in length, that are highly conserved and noncoding. They play a crucial role in gene expression regulation following transcription by specifically binding to complementary target messenger RNAs (mRNAs).…”

Section: Introductionmentioning

confidence: 99%

Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain

Sabattini,

Baldassarro,

Zaccone

et al. 2023

Vet Comparative Oncology

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Haemangiosarcoma is a highly metastatic and lethal cancer of blood vessel‐forming cells that commonly spreads to the brain in both humans and dogs. Dysregulations in phosphatase and tensin (PTEN) homologue have been identified in various types of cancers, including haemangiosarcoma. MicroRNAs (miRNAs) are short noncoding single‐stranded RNA molecules that play a crucial role in regulating the gene expression. Some miRNAs can function as oncogenes or tumour suppressors, influencing important processes in cancer, such as angiogenesis. This study aimed to investigate whether miRNAs targeting PTEN were disrupted in canine haemangiosarcoma and its corresponding brain metastases (BM). The expression levels of miRNA‐10b, miRNA‐19b, miRNA‐21, miRNA‐141 and miRNA‐494 were assessed in samples of primary canine cardiac haemangiosarcomas and their matched BM. Furthermore, the miRNA profile of the tumours was compared to samples of adjacent non‐cancerous tissue and healthy control tissues. In primary cardiac haemangiosarcoma, miRNA‐10b showed a significant increase in expression, while miRNA‐494 and miRNA‐141 exhibited downregulation. Moreover, the overexpression of miRNA‐10b was retained in metastatic brain lesions. Healthy tissues demonstrated significantly different expression patterns compared to cancerous tissues. In particular, the expression of miRNA‐10b was nearly undetectable in both control brain tissue and perimetastatic cerebral tissue. These findings can provide a rationale for the development of miRNA‐based therapeutic strategies, aimed at selectively treating haemangiosarcoma.

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Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy

Wani,

Singh,

Akhtar

et al. 2024

MRMC

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Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients.

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Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma

Cited by 5 publications

References 43 publications

New molecular targets in canine hemangiosarcoma—Comparative review and future of the precision medicine

New molecular targets in canine hemangiosarcoma—Comparative review and future of the precision medicine

Dysregulated miRNAs in a canine model of haemangiosarcoma metastatic to the brain

Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy

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