Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy.

Thyroid cancer represents a heterogenous disease whose incidence has increased in the last decades. Although three main different subtypes have been described, molecular characterization is progressively being included in the diagnostic and therapeutic algorithm of these patients. In fact, thyroid cancer is a landmark in the oncological approach to solid tumors as it harbors key genetic alterations driving tumor progression that have been demonstrated to be potential actionable targets. Within this promising and rapid changing scenario, current efforts are directed to improve tumor characterization for an accurate guidance in the therapeutic management. In this sense, it is strongly recommended to perform tissue genotyping to patients that are going to be considered for systemic therapy in order to select the adequate treatment, according to recent clinical trials data. Overall, the aim of this article is to provide a comprehensive review on the molecular biology of thyroid cancer focusing on the key role of tyrosine kinases. Additionally, from a clinical point of view, we provide a thorough perspective, current and future, in the treatment landscape of this tumor.

Targeting Angiogenesis in Pancreatic Neuroendocrine Tumors: Resistance Mechanisms.

Despite being infrequent tumors, the incidence and prevalence of pancreatic neuroendocrine tumors (P-NETs) has been rising over the past few decades. In recent years, rigorous phase III clinical trials have been conducted, allowing the approval of several drugs that have become the standard of care in these patients. Although various treatments are used in clinical practice, including somatostatin analogues (SSAs), biological therapies like sunitinib or everolimus, peptide receptor radionuclide therapy (PRRT) or even chemotherapy, a consensus regarding the optimal sequence of treatment has not yet been reached. Notwithstanding, sunitinib is largely used in these patients after the promising results shown in SUN111 phase III clinical trial. However, both prompt progression as well as tumor recurrence after initial response have been reported, suggesting the existence of primary and acquired resistances to this antiangiogenic drug. In this review, we aim to summarize the most relevant mechanisms of angiogenesis resistance that are key contributors of tumor progression and dissemination. Furthermore, several targeted molecules acting selectively against these pathways have shown promising results in preclinical models, and preliminary results from ongoing clinical trials are awaited.

BRAF Mutated Colorectal Cancer: New Treatment Approaches.

Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.), which result in prognostic factors. Different molecular subtypes have been identified, according to genomic and transcriptomic criteria. A subgroup harboring a BRAF mutation has been described, and represents approximately 10% of the patients diagnosed with colon cancer. This subgroup has morphological, clinical, and therapeutic characteristics that differ substantially from patients who do not carry this genetic alteration. Unfortunately, there is no established standard of care for this particular cohort of patients. This manuscript aims to study the biology of this subgroup of colon cancer, to understand the current approach in clinical research.