Tumor Microenvironment-Associated Pericyte Populations May Impact Therapeutic Response in Thyroid Cancer.

Asumi Iesato, Carmelo Nucera

Journal: Advances in experimental medicine and biology 2021;1329():253-269

PMID: 34664244

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Abstract

Thyroid cancer is the most common endocrine malignancy, and aggressive radioactive iodine refractory thyroid carcinomas still lack an effective treatment. A deeper understanding of tumor heterogeneity and microenvironment will be critical to establishing new therapeutic approaches. One of the important influencing factors of tumor heterogeneity is the diversity of cells in the tumor microenvironment. Among these are pericytes, which play an important role in blood vessel stability and angiogenesis, as well as tumor growth and metastasis. Pericytes also have stem cell-like properties and are a heterogeneous cell population, and their lineage, which has been challenging to define, may impact tumor resistance at different tumor stages. Pericytes are also important stroma cell types in the angiogenic microenvironment which express tyrosine-kinase (TK) pathways (e.g., PDGFR-β). Although TK inhibitors (TKI) and BRAF inhibitors are currently used in the clinic for thyroid cancer, their efficacy is not durable and drug resistance often develops. Characterizing the range of distinct pericyte populations and distinguishing them from other perivascular cell types may enable the identification of their specific functions in the thyroid carcinoma vasculature. This remains an essential step in developing new therapeutic strategies. Also, assessing whether thyroid tumors hold immature and/or mature vasculature with pericyte populations coverage may be key to predicting tumor response to either targeted or anti-angiogenesis therapies. It is also critical to apply different markers in order to identify pericyte populations and characterize their cell lineage. This chapter provides an overview of pericyte ontogenesis and the lineages of diverse cell populations. We also discuss the role(s) and targeting of pericytes in thyroid carcinoma, as well as their potential impact on precision targeted therapies and drug resistance.

Address: Human Thyroid Cancers Preclinical and Translational Research Program, Division of Experimental Pathology, Cancer Research Institute, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Center for Vascular Biology Research (CVBR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Human Thyroid Cancers Preclinical and Translational Research Program, Division of Experimental Pathology, Cancer Research Institute, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. [email protected].; Center for Vascular Biology Research (CVBR), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. [email protected].; Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].

DOI: 10.1007/978-3-030-73119-9_14