Available evidence and new biological perspectives on medical treatment of advanced thymic epithelial tumors.

Thymic epithelial tumors (TETs) are rare primary mediastinal tumors arising from thymic epithelium. Their rarity and complexity hinder investigations of their causes and therapy development. Here, we summarize the existing knowledge regarding medical treatment of these tumors, and thoroughly review the known genetic aberrations associated with TETs and the present status of potential biological treatments. Epidermal growth factor receptor (EGFR), stem-cell factor receptor, insulin-like growth factor-1 receptor (IGF1R), and vascular endothelial growth factors (VEGF-A, VEGF-B, and VEGF-2) are overexpressed in TETs. EGFR overexpression in TETs is associated with higher stage, and IGF1R overexpression has poor prognostic value. Data indicate that anti-IGF1R monoclonal antibodies, and inhibitors of angiogenesis, somatostatin receptors, histone deacetylase, mammalian target of rapamycin, and cyclin-dependent kinases may be active against TETs. Continued investigations in this field could lead to advancement of targeted and biological therapies for TETs.

Targeted therapy-induced diarrhea: A review of the literature.

PURPOSE OF RESEARCH: Revision of the literature on targeted therapy-induced diarrhea (TT-ID). PRINCIPAL RESULTS: TT-ID is frequent; the mechanisms are mainly secretive, followed by ischemic or autoimmune ones. The duration of TT-ID is protracted over time. Its intensity is of grade G1-G3 but may be fatal in patients with diffuse colitis or on ipilimumab. However, no specific guidelines are available on management of different grades of TT-ID. Preventive measures with antibiotics, probiotics or activated charcoal should be further investigated. Loperamide is the first choice drug followed by octreotide. The role of corticosteroids is controversial. CONCLUSION: Early assessment and management of TT-ID is essential to prevent the worsening of this side-effect, patients' hospitalization and dose reduction or oncological treatment discontinuation. Future research is needed to better understand the pathophysiological mechanisms of TT-ID and it should also be investigated whether a specific pharmacological and/or non pharmachological approach is indicated.

Targeting the MET gene for the treatment of non-small-cell lung cancer.

Recently, a better understanding of the specific mechanisms of oncogene addiction has led to the development of antitumor strategies aimed at blocking these abnormalities in different malignancies, including lung cancer. These abnormalities trigger constitutive activation of tyrosine kinase receptors (RTKs) involved in fundamental cell mechanisms such as proliferation, survival, differentiation and migration, and consequently the aberrant signaling of RTKs leads to cancer growth and survival. The inhibition of aberrant RTKs and downstream signaling pathways has opened the door to the targeted therapy era. In non-small-cell lung cancer (NSCLC), molecular research has allowed the discrimination of different aberrant RTKs in lung cancer tumorigenesis and progression, and thus the identification of several targetable oncogenic drivers. Following the development of small molecules (gefitinib/erlotinib and crizotinib) able to reversibly inhibit the epidermal growth factor receptor (EGFR) and signaling pathways mediated by anaplastic lymphoma kinase (ALK), respectively, the MET signaling pathway has also been recognized as a potential target. Moreover, according to current knowledge, MET could be considered both as a secondary oncogenic mechanism and as a prognostic factor. Several therapeutic strategies for inhibiting activated hepatocyte growth factor receptor (HGFR) and the subsequent downstream signaling transduction have been improved in order to block tumor growth. This review will focus on the MET pathway and its role in resistance to EGFR TK (tyrosine kinase) inhibitors, the different strategies of its inhibition, and the potential approaches to overcoming acquired resistance.