Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer

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.

Tumor-Associated Macrophage Status in Cancer Treatment

“…The use of virotherapy is emerging as a valid therapeutic treatment for several type of cancer. It is based on the use of OVs that, beyond their direct lytic effect on tumor cells, function through a multitude of events like modification of the tumor micro/macro-environment, modulation of the antitumor immune response [6][7][8][9]. The role of macrophages on virotherapy efficacy varies according to the tumor model.…”

“…Additionally, TAMs are mainly responsible for resistance to well-known antitumor treatments like chemotherapy and radiotherapy, indeed they limit the efficacy of immunotherapy, i.e., anti-PD1 treatment [3][4][5]. However, depending on the tumor type and treatment adopted it might be possible to identify novel approaches, i.e., combinatory therapies also taking advantage of more recent treatments as those based on the use of oncolytic viruses (OV) [6][7][8][9]. In this review, we will highlight TAMs as therapeutic target and their modulation by anticancer therapies.…”

PD-1 Blockade Delays Tumor Growth by Inhibiting an Intrinsic SHP2/Ras/MAPK Signalling in Thyroid Cancer Cells

“…By contrast, aggressive forms of TC (PDTC and ATC) represent a clinic challenge displaying a remarkable chemo-and radio-resistant phenotype from the beginning [9,10]. Interestingly, aggressive forms of TC exhibit increased immune checkpoint expression and ine cient immune in ltrate [9,[11][12][13][14], features that are being evaluated for the treatment of the disease [9,14,15].…”

Reply to Comment on “Malfitano, A.M. et al. Virotherapy as a Potential Therapeutic Approach for the Treatment of Aggressive Thyroid Cancer” Cancers 2019, 11, 1532

“…Therefore, we provide a brief description of the overall use of OVs in the clinic. Rigvir is among the few OVs that have already been used for the treatment of patients, and studies describing its effects have been briefly commented and cited in our text [1].…”