Abstract
Virotherapy is a novel cancer treatment based on oncolytic viruses (OVs), which selectively infect and lyse cancer cells, without harming normal cells or tissues. Several viruses, either naturally occurring or developed through genetic engineering, are currently under investigation in clinical studies. Emerging reports suggesting the immune-stimulatory property of OVs against tumor cells further support the clinical use of OVs for the treatment of lesions lacking effective therapies. Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), have a poor prognosis and limited treatment options. Therefore, several groups investigated the therapeutic potential of OVs in PDTC/ATC models producing experimental data sustaining the potential clinical efficacy of OVs in these cancer models. Moreover, the presence of an immunosuppressive microenvironment further supports the potential use of OVs in ATC. In this review, we present the results of the studies evaluating the efficacy of OVs alone or in combination with other treatment options. In particular, their potential therapeutic combination with multiple kinases inhibitors (MKIs) or immune checkpoint inhibitors are discussed.
Highlights
Thyroid carcinoma (TC) is the most common endocrine malignancy
These datas were confirmed by other studies showing that (i) high PD-L1 levels in Papillary thyroid carcinoma (PTC) were correlated with tumor-associated macrophages (TAM) and lymphocytic infiltrate [133,134]; (ii) the expression of PD-L1 was significantly associated with increased tumor size and multifocality of Poorly differentiated thyroid carcinoma (PDTC); (iii) PD-1+ T-lymphocytes were associated with cancer lymph-nodal invasion and recurrent disease [135]
Multimodality treatments have not increased the survival rate and the use of multiple kinases inhibitors (MKIs) targeting the signaling pathways activated in TC have limited benefits
Summary
Thyroid carcinoma (TC) is the most common endocrine malignancy. Its incidence is estimated to be 1–2 million per year [1,2]. ATC and PDTC are tumors that lose, completely or partially, the typical features of their original follicular cells. Genetic analysis of these tumors demonstrated that ATC, and to a lesser extent PDTC, accumulate several different oncogenic alterations, TERT oncogene and TP53 tumor suppressor gene are the most frequently altered genes. Undifferentiated TCs are characterized by a rapid tumor growth, trachea obstruction with respiratory distress, and frequent distant metastases, with a survival time of six months from the diagnosis. For these forms multimodal treatment, surgery, chemotherapy, and radiation obtained a very limited success [1,2,4,5]. We focused on reports dealing with the use of OVs in TC
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