Improving Cancer Therapeutics by Molecular Profiling

Abstract

The individualized medicine aims to identify the molecular basis of the individual's response to different therapeutic treatments. Individualized medicine is very relevant for human diseases such as cancer and it has become a major task to accomplish more efficient and specific therapeutics. An individualized response to treatment could underline therapeutic success or failure and, even more, could support the rationale for good or bad prognosis. The use of up to date genomic approaches is changing the way we understand modern medicine in terms of drug efficacy, toxicity and diagnosis. Results from genetic polymorphism studies, gene expression profiling and epigenetics illustrate how pharmacogenomic testing will contribute to the goal of individualized medicine. Antineoplastic drugs are designed to block the anomalous activity of specific molecules (therapeutic targets) that regulate cellular processes such as cell cycle. Understanding the relationship between molecular changes in therapeutic targets and enhanced antitumoral response or chemotherapeutic resistance is crucial to establish the clinical relevance of genomic approaches. The goal of this review is to discuss the basic and the clinical significance of genomic research on drug targets and its impact on the early diagnosis and treatment of cancer. We will also assess how these methodologies could contribute to individualized medicine in oncology. A special focus will be put on oncogenes and tumor suppressor genes. Aspects such as drug efficacy, side effects and the diagnostic value of antineoplastic pharmacogenomic research will be also considered.

New Trends in Aryl Hydrocarbon Receptor Biology

“…In agreement with a positive effect of AhR in liver growth, AhR-/- mice show reduced liver size, portal fibrosis and impaired induction of detoxifying enzymes that could compromise its function (Fernandez-Salguero et al, 1995 ; Peterson et al, 2000 ; Corchero and Fernández-Salguero, 2005 ). Some of these phenotypes in AhR-null livers appear to be related to the over-activation of TGFβ due to the up-regulation in the extracellular matrix of its latency protein LTBP-1, which was in fact identified as a novel AhR target gene (Santiago-Josefat et al, 2004 ; Corchero and Fernández-Salguero, 2005 ; Gomez-Duran et al, 2006 , 2008 ). The scenario in the liver appears more complex since AhR also regulates RA levels and retinoid homeostasis (Andreola et al, 1997 , 2004 ), which are functionally related to TGFβ and to cell growth and differentiation.…”