The Thyroid Tumor Microenvironment: Potential Targets for Therapeutic Intervention and Prognostication

Abstract

Thyroid cancer is the most common endocrine malignancy and incidences are rising rapidly, in both pediatric and adult populations. Many thyroid tumors are successfully treated which results in low mortality rates, but there is often a significant morbidity associated with thyroid cancer treatments. For patients with tumors that are not successfully treated with surgical resection or radioactive iodine treatment, prognosis is dramatically reduced. Patients diagnosed with anaplastic thyroid cancer face a very grim prognosis with a median survival of 6 months post-diagnosis. There is a critical need to identify patients who are at greatest risk of developing persistent disease and progressing to poorly differentiated or anaplastic disease. Furthermore, development of treatments associated with less morbidity would represent a significant improvement for thyroid cancer survivors. It is well established the stromal cells and components of the tumor microenvironment can drive tumor progression and resistance to therapy. Here we review the current state of what is known regarding the thyroid tumor microenvironment and how these factors may contribute to thyroid tumor pathogenesis. Study of the tumor microenvironment within thyroid cancer is a relatively new field, and more studies are needed to dissect the complex and dynamic crosstalk between thyroid tumor cells and its tumor niche.

Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies

“…In brief, the work on the HECT E3s expands our understanding of the pathogenesis of hematological diseases, providing novel effectors, whose biological significance and therapeutic interest might be explored in the future, especially considering the development of precision oncology [100][101][102]. This field has opened several novel opportunities, thanks to new algorithms [103][104][105] and artificial intelligence [106], modernizing the field of precision oncology in general [107][108][109] as well as in specific cancers [110][111][112][113]. From this overview, it appears clear that further studies are needed to corroborate the implications of HECT-type E3s in leukemogenesis, to understand the molecular basis of their oncogenic function in hematological disorders, as well as to identify their relevant substrates and regulators.…”

Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

“…Over the last 20 years, the role of the microenvironment in tumorigenesis of thyroid cancer has been well-defined [15]. The components of the thyroid cancer microenvironment (stromal cells, ST, and extracellular matrix components (ECM)) surround and support cancer cells, interacting with them by direct cell-cell and cell-extracellular matrix components interaction.…”

“…MMP-9 expression is upregulated in PTC and might be a prognostic indicator for more advanced-stage cancer [139][140][141][142]. The prognostic role of other components of the extracellular matrix of thyroid cancer tangentially involved in angiogenetic processes, such as macrophages and T lymphocytes, is yet to be clarified [15].…”

Central vascular ligation and mesentery based abdominal surgery

“…Furthermore, in recent years, the concept of CME with dissection adhering to embryological planes and central vascular ligation (CVL) has also been adopted to colonic resection [106,107]. This will certainly affect the current value of current prognostic markers [108][109][110][111][112][113] that are essential for a modern precision oncology [114][115][116][117][118][119][120][121] The "complete mesopancreas excision", instead, is not similar to "complete mesocolon" or "total mesorectal" excision [122]. Extended lymphadenectomy has no survival benefit for patients with pancreatic cancer.…”