Abstract
Aggressive pituitary tumors account for up to 10% of pituitary tumors and are characterized by resistance to medical treatment and multiple recurrences despite standard therapies, including surgery, radiotherapy, and chemotherapy. They are associated with increased morbidity and mortality, particularly pituitary carcinomas, which have mortality rates of up to 66% at 1 year after diagnosis. Novel targeted therapies under investigation include mammalian target of rapamycin (mTOR), tyrosine kinase, and vascular endothelial growth factor (VEGF) inhibitors. More recently, immune checkpoint inhibitors have been proposed as a potential treatment option for pituitary tumors. An increased understanding of the molecular pathogenesis of aggressive pituitary tumors is required to identify potential biomarkers and therapeutic targets. This review discusses novel approaches to the management of aggressive pituitary tumors and the role of molecular profiling.
Highlights
Pituitary tumors account for approximately 10% to 15% of all intracranial tumors [1], with a prevalence of clinically significant pituitary tumors reported as 80 to 100 cases per 100,000 [2]
Increased vascular endothelial growth factor (VEGF) expression in APT compared with non-aggressive pituitary tumors
Aggressive pituitary tumor (APT), pituitary carcinoma (PC), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) progression free survival (PFS), overall survival (OS), colorectal cancer (CRC), renal cell carcinoma (RCC), growth hormone (GH), epidermal growth factor receptor (EGFR), monoclonal antibodies, tyrosine kinase inhibitors (TKIs), fibroblast growth factor (FGF), fibroblast growth factor receptor (FGFR), pituitary adenoma (PA), non-functioning pituitary adenomas (NFPAs), basal cell carcinoma (BCC), sonic hedgehog (SHH), pituitary tumor transforming gene (PTTG), DNA methyltransferase (DNMT), histone deacetylase (HDAC), EGF containing fibulin-like extracellular matrix protein (EFEMP1), high mobility group A (HMGA), immune checkpoint inhibitor (ICI), programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), cytotoxic T lymphocyte associated protein 4 (CTLA4)
Summary
Pituitary tumors account for approximately 10% to 15% of all intracranial tumors [1], with a prevalence of clinically significant pituitary tumors reported as 80 to 100 cases per 100,000 [2]. Atypical adenomas were defined as tumors with histological features suggestive of aggressive clinical behavior, including an elevated mitotic index, proliferation marker Ki-67 labeling index >3%, and overexpression of tumour protein p53 by immunohistochemistry [4]. It has been more recently proposed that APT be defined clinically as invasive tumors displaying an unusually rapid tumor growth rate or tumor growth despite optimal standard therapies, including surgery, radiotherapy, and chemotherapy [1,2,3]. In the management of APTs and PCs, the use of novel targeted therapies has emerged somewhat incidentally on the back of successful application in other cancer types. We will review the role of novel targeted therapies and initial experience with immunotherapy in the management of APT and PC and propose a focus on the development of molecular profiling of these tumors to help rationalize treatment modalities
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