ROS1 mutation and treatment with crizotinib in a 30-year old Caucasian woman with stage IV non-small cell lung cancer/adenocarcinoma and complete remission.

In this case report we describe a 30 year-old Caucasian woman with a histopathological diagnosis of pulmonary adenocarcinoma in both lungs with lipidic and micropapillary growth pattern and ROS1 (C-ros oncogene 1, receptor tyrosine kinase) rearrangement. There is evidence that crizotinib can be used for molecular target therapy in these patients. We enrolled the patient in an off-label program for the treatment of ROS1 rearranged adenocarcinomas with the EML4/anaplastic lymphoma kinase inhibitor crizotinib. After a follow-up of eight weeks we saw a complete remission in both lungs without any signs of metabolic tumor activity. This report shows the importance of testing young patients with adenocarcinomas of the lung for rare oncogenic driver mutations, such as ROS1, with possible molecular treatment options.

Current and future treatment options in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown aetiology with deteriorating respiratory function leading to respiratory failure. Sequential acute lung injury leads to progressive fixed tissue fibrosis, architectural distortion and loss of function. An excess of profibrotic cytokines and/or a deficiency in antifibrotic cytokines have been implicated in the pathological process as has excessive oxidation. At present no specific therapy is available. Corticosteroids alone or in combination with immunosuppressive drugs such as azathioprine, colchicine, and cyclophosphamide have been used with limited success. Interferon-gamma-1b showed a significant improvement in pulmonary function only in one study. Pirfenidone, cyclosporine and acetylcysteine may also prove to be of benefit but data from studies are limited. Novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. Most recently, endothelin receptor antagonists (eg. bosentan) have been shown to have possible beneficial effects in early stages of IPF. After a short overview on the current hypothesis on pathophysiology in IPF this review will discuss the present and possible future therapeutic options in IPF.

Vasoproliferation and antiproliferative treatment options in pulmonary arterial hypertension.

New treatment options have improved the prognosis of patients with pulmonary arterial hypertension. However, drugs such as prostanoids, PDE5 inhibitors and endothelin receptor antagonists mainly act as vasodilating agents. Recently, it has become clear that pulmonary arterial hypertension is an inflammatory and vasoproliferative disease. Therefore new anti-inflammatory and antiproliferative treatments are needed. This review will focus on the pathogenesis of inflammation and vasoproliferation in pulmonary hypertension. In addition, an overview on possible new antiinflammatory and antiproliferative drugs in pulmonary hypertension (e.g. Rho-kinase inhibitors, imatinib mesylate. HMG-CoA reductase inhibitors) will be given along with recent patents.

Sarcomatoid carcinomas of the lung--are these histogenetically heterogeneous tumors?

Sarcomatoid carcinomas (SC) of the lung are a heterogeneous group of nonsmall cell lung carcinomas (NSCLC) containing a sarcoma or sarcoma-like component. SC may represent an epithelial neoplasm undergoing divergent tissue differentiation originating from a single clone. Epithelial-mesenchymal transition (EMT) best describes the origin of the spindle and giant cells. We aimed to define chromosomal aberrations within the subgroups of SC and if EMT does play a role in SC. Twenty-two SC were investigated by chromosomal comparative genomic hybridization (CGH). Immunohistochemical staining was performed with antibodies for E-cadherin, Vimentin, c-Fos, c-Jun, Snail, TGFbeta1, Notch1, beta-catenin, Glycogen synthase kinase 3beta (GSK3beta), and Fascin. Gains occurred more frequently than losses (70.5 vs 29.5%). The shortest regions of overlap were gains on chromosomes 8q and 7 followed by 1q, 3q, and 19, supporting the common origin of the different subtypes of SC. The immunohistochemical staining suggests that the sarcomatoid components of SC might have undergone EMT, not triggered by the signaling pathways Notch1, Snail, and TGFbeta1, but probably initiated by an upregulation of c-Jun and a consecutive overexpression of Vimentin and Fascin. The Wnt-pathway was not deregulated because combined membrane and cytoplasmic reactivity for beta-catenin and GSK3beta was observed.