Affiliation:
1. Inserm U1052, CNRS UMR5286, Cancer Research Center of Lyon , 69373 Lyon , France
2. Lyon 1 University , 69100 Villeurbanne , France
3. Endocrinology Department, “C.I. Parhon” National Institute of Endocrinology , 011684 Bucharest , Romania
4. Pathology Department, Reference Center for Rare Pituitary Diseases HYPO, “Groupement Hospitalier Est” Hospices Civils de Lyon , 69677 Bron , France
5. Endocrinology Department, Reference Center for Rare Pituitary Diseases HYPO, “Groupement Hospitalier Est” Hospices Civils de Lyon , 69677 Bron , France
Abstract
AbstractPituitary adenomas (PAs) are neoplasms derived from the endocrine cells of the anterior pituitary gland. Most frequently, they are benign tumors, but may sometimes display an aggressive course, and in some cases metastasize. Their biology, including their wide range of behavior, is only partly understood. In terms of therapeutic targeting, most PAs are easily treated with available medical treatments, surgery, and sometimes radiotherapy. Nevertheless, gonadotroph adenomas lack medical therapeutic options, and treatment of aggressive PAs and pituitary carcinomas remains challenging. Here, we present an overview of the implications of the tumor microenvironment in PAs, reviewing its composition and function, as well as published cases that have been treated thus far using tumor microenvironment–targeting therapies. Additionally, we discuss emerging views, such as the concept of nonangiogenic tumors, and present perspectives regarding treatments that may represent future potential therapeutic options. Tumor-infiltrating lymphocytes, tumor-associated macrophages, folliculostellate cells, tumor-associated fibroblasts, angiogenesis, as well as the extracellular matrix and its remodeling, all have complex roles in the biology of PAs. They have been linked to hormone production/secretion, size, invasion, proliferation, progression/recurrence, and treatment response in PAs. From a therapeutic perspective, immune-checkpoint inhibitors and bevacizumab have already shown a degree of efficacy in aggressive PAs and pituitary carcinomas, and the use of numerous other tumor microenvironment-targeting therapies can be foreseen. In conclusion, similar to other cancers, understanding the tumor microenvironment improves our understanding of PA biology beyond genetics and epigenetics, and constitutes an important tool for developing future therapies.
Funder
Fondation ARC pour la recherche sur le cancer
Ligue contre le cancer
Région Rhone-Alpes-Auvergne
Société Française d’Endocrinologie
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism