Dr. Munir R. Tanas of the University of Iowa said, “Sarcomas are difficult to treat when malignant mesenchymal neoplasms appear in bone or soft tissue.”

Oncotarget released “Prognostic and therapeutic value of the Hippo-Pathway, RABL6A and p53-MDM2 axes in sarcomas”, Who reported that the authors here evaluate the expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with possible binding to both pathways, in sarcomas of various histological types.

Immunohistochemical staining of a tissue microarray with 163 sarcomas and the correlation with clinical data showed that increased YAP and TAZ values ​​independently predict poor overall survival and progression-free survival, respectively.

In the absence of p53 expression, the combined TAZ and YAP expression influences overall survival, progression-free and metastasis-free survival more than TAZ or YAP activation alone.

RABL6A independently predicted a shorter time to metastasis and positively correlated with p53, MDM2, and YAP expression, supporting a possible functional relationship between the biomarkers.

The network analysis also showed that TAZ correlates positively with MDM2 expression.

Dr. Munir R. Tanas of the University of Iowa said: “Sarcomas are difficult-to-treat malignant mesenchymal neoplasms that occur in bone or soft tissue.

In epithelial hemangioendothelioma, a vascular sarcoma, a WWTR1-CAMTA1 gene fusion encodes a constitutively activated form of TAZ that activates a TAZ-like transcription program.

Alterations in the p53 signaling pathway are among the most common aberrations seen in human cancers, including sarcomas.

The most common types of tumors found in people with LFS include sarcomas, especially soft tissue sarcomas and osteosarcomas.

Therefore, amplification of the MDM2 gene region in several sarcomas, including well-differentiated liposarcoma / dedifferentiated liposarcoma, parostal and low-grade central osteosarcoma, and intimal sarcomas, is an effective mechanism of p53 inactivation.

RABL6A is a newly identified oncoprotein implicated in a variety of human cancers, including pancreatic neuroendocrine tumors, breast cancer, colon cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, and osteosarcoma.

The Tanas research team concluded in their oncotarget research result: “We expect combination therapies that target this network to be most effective in treating sarcomas. In addition, there is a need to further validate these RABL6A / YAP / p53 and TAZ / MDM2 expression signatures in a larger number of different histological sarcoma types to determine whether they predict differently the prognosis or response to therapy within individual subsets of these sarcomas . We anticipate that these efforts above will result in a more effective, tailored approach to these cancers for which few effective medical therapies are currently available.


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DOI – https: //.doi.org /10.18632 /oncotarget.27928

Full text – https: //.www.oncotarget.com /Items/27928 /Text/

Correspondence – Munir R. Tanas – [email protected]

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