Increasing understanding of molecular carcinogenesis has begun to change paradigms in oncology. On the diagnostic side, the characterization of key mutations and molecular pathways responsible for tumor development and progression has led to the identification of a large number of potential targets for diagnostic and therapeutic intervention.

On the treatment and prevention side, molecular analysis will be of even greater importance for guiding individualized therapy. Diagnostics of molecular lesions present in each tumor will become a key feature of future clinical care. This will allow prediction of response with substantially increased accuracy, stratification of particular patient groups, and eventually personalization of therapy. Striking examples of molecular targeted therapies that have already been established in clinical practice include tyrosine kinase inhibitors in chronic myelogenous leukemia and gastrointestinal stromal tumors, epidermal growth factor receptor (EGFR) inhibition in EGFR-mutated lung cancer, HER2/neu blockade in HER2/neu-positive breast cancer, and anaplastic lymphoma kinase (ALK) inhibitors in lung cancer with EML4-ALK fusion.

The scientific development along this line will change the approach to tumor diseases in the future. Patients will be treated according to the specific molecular profiles found in the individual tumor tissue and preferentially with targeted substances, if available.

Idiopathic pulmonary fibrosis (IPF) is a devastating and progressive lung disease. Its aetiology is thought to involve damage to the epithelium and abnormal repair. Alveolar epithelial cells near areas of remodelling show an increased expression of proapoptotic molecules. Therefore, we investigated the role of genes involved in cell cycle control in IPF.

Genotypes for five single nucleotide polymorphisms (SNPs) in the tumour protein 53 (TP53) gene and four SNPs in cyclin-dependent kinase inhibitor 1A (CDKN1A), the gene encoding p21, were determined in 77 IPF patients and 353 controls. In peripheral blood mononuclear cells (PBMC) from 16 healthy controls mRNA expression of TP53 and CDKN1A was determined.Rs12951053 and rs12602273, in TP53, were significantly associated with survival in IPF patients. Carriers of a minor allele had a 4-year survival of 22% versus 57% in the non-carrier group (p = 0.006). Rs2395655 and rs733590, in CDKN1A, were associated with an increased risk of developing IPF. In addition, the rs2395655 G allele correlated with progression of the disease as it increased the risk of a rapid decline in lung function. Functional experiments showed that rs733590 correlated significantly with CDKN1A mRNA expression levels in healthy controls.This is the first study to show that genetic variations in the cell cycle genes encoding p53 and p21 are associated with IPF disease development and progression.

These findings support the idea that cell cycle control plays a role in the pathology of IPF. Variations in TP53 and CDKN1A can impair the response to cell damage and increase the loss of alveolar epithelial cells.

Thioredoxin system is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. It includes thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. Trx plays an essential role in cell function by limiting oxidative stress directly via antioxidant effects and indirectly by proteins interaction with key signal transduction molecules.

A variety of signaling molecules have been implicated in the cytoprotection conferred by Trx, such as autophagic proteins, p38 mitogen-activated protein kinase, nuclear factor-κB, phosphatidylinositol 3-kinase. Recent studies indicated that Trx may contribute to the pathogenesis of COPD, asthma and lung injury. Enhanced Trx expression or application of recombinant Trx afforded protection in preclinical models of pulmonary tissue injury, which suggested Trx may be used in future therapeutic applications.

The focus of this review is on the significance of Trx in various pulmonary diseases, which as a potential therapeutic strategy to protect against oxidative stress and inflammation.

advances in stem cell research and tissue engineering have opened new paradigms for future therapies toward many intractable diseases. Many tissue engineering approaches are also applied in the pulmonary research field.

Several materials have been utilized as scaffolds to support lung tissue engineering to recapitulate the three-dimensional (3D) structure of the lung. Natural products and synthetic polymers are the two major components of the scaffold materials. Decellularization of allogeneic or xenogenic donor lungs is also utilized to obtain biological 3D matrix scaffolds. Decellularized lungs are recellularized with stem or progenitor cells.

Cell sources are the key components for tissue engineering. The best cell source for tissue engineering is autologous cells obtained from patients because it does not induce an immunological response after transplantation. However, the stem/progenitor population in adult organs is generally small, and their capacity for proliferation or differentiation is limited.

Knowledge about the endogenous stem/progenitor population in lung tissue has been expanded recently. Although the lung is the most challenging organ for tissue engineering because of its complex 3D structure and more than 40 different cell types, several breakthroughs in respiratory research have been made.

These results give us a greater understanding of the possibilities and the limitations of tissue engineering for pulmonary diseases. © 2012 The Author. Respirology © 2012 Asian Pacific Society of Respirology.