Review
Abstract
Lung cancer is the leading cause of cancer death worldwide. The disease is particularly difficult to detect, and patients often present at an advanced stage. Current treatments have limited effectiveness, and unfortunately, the prognosis remains poor. Recent insights into the molecular pathogenesis and biologic behavior of lung cancer have led to the development of rationally designed methods of early detection, prevention, and treatment of this disease. This article will review the important clinical implications of these advances, with a focus on new molecularly targeted therapies currently in development.
Authors
Sophie Sun, Joan H. Schiller, Monica Spinola, John D. Minna
Abstract
Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer prevalence increases, challenges remain in the diagnosis of clinically relevant prostate cancer as well as the management of the metastatic and androgen-independent metastatic disease states.
Authors
Russel S. Taichman, Robert D. Loberg, Rohit Mehra, Kenneth J. Pienta
Abstract
Substantial evidence shows that neoplastic and nonneoplastic tissue growth is dependent on angiogenesis. Neovascularization and adipogenesis are temporally and spatially coupled processes during prenatal life and they continue to reciprocally interact via paracrine signaling systems throughout adult life. Activated adipocytes produce multiple angiogenic factors including leptin, angiopoietins, HGF, GM-CSF, VEGF, FGF-2, and TGF-β, which either alone or collectively stimulate neovascularization during fat mass expansion. Thus antiangiogenic agents provide a novel therapeutic option for prevention and treatment of human obesity and its related disorders.
Authors
Yihai Cao
Abstract
MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Recent studies have revealed key roles of microRNAs as regulators of the growth, development, function, and stress responsiveness of the heart, providing glimpses of undiscovered regulatory mechanisms and potential therapeutic targets for the treatment of heart disease.
Authors
Eva van Rooij, Eric N. Olson
Abstract
Understanding the genetic origin of cancer at the molecular level has facilitated the development of novel targeted therapies. Aberrant activation of the ErbB family of receptors is implicated in many human cancers and is already the target of several anticancer therapeutics. The use of mAbs specific for the extracellular domain of ErbB receptors was the first implementation of rational targeted therapy. The cytoplasmic tyrosine kinase domain is also a preferred target for small compounds that inhibit the kinase activity of these receptors. However, current therapy has not yet been optimized, allowing for opportunities for optimization of the next generation of targeted therapy, particularly with regards to inhibiting heteromeric ErbB family receptor complexes.
Authors
Hongtao Zhang, Alan Berezov, Qiang Wang, Geng Zhang, Jeffrey Drebin, Ramachandran Murali, Mark I. Greene
Abstract
Many lessons in autoimmunity — particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology — can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell–mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.
Authors
Amos Gilhar, Ralf Paus, Richard S. Kalish
Abstract
The scientists of today have become accustomed to the extremely rapid pace of progress in the biomedical sciences spurred on by the discovery of recombinant DNA and the advent of automated DNA sequencing and PCR, with progress usually being measured in months or years at most. What is often forgotten, however, are the many prior advances that were needed to reach our present state of knowledge. Here I illustrate this by discussing the scientific discoveries made over the course of the past century and a half that ultimately led to the recent successful development of drugs, particularly imatinib mesylate, to treat chronic myelogenous leukemia.
Authors
Tony Hunter
Abstract
Almost 50 years ago, David Hungerford and I noticed an abnormally small chromosome in cells from patients with chronic myelogenous leukemia (CML). This article is a personal perspective of the events leading to the discovery of this chromosome, which became known as the Philadelphia chromosome. As technology advanced over subsequent decades, the translocation resulting in the Philadelphia chromosome has been identified, its role in the development of CML has been confirmed, and a therapy directed against the abnormal protein it produces has shown promising results in the treatment of patients with CML.
Authors
Peter C. Nowell
Abstract
The identification of the Philadelphia chromosome in cells from individuals with chronic myelogenous leukemia (CML) led to the recognition that the BCR-ABL tyrosine kinase causes CML. This in turn led to the development of imatinib mesylate, a clinically successful inhibitor of the BCR-ABL kinase. Incorporating the use of markers of BCR-ABL kinase inhibition into clinical trials led to the realization that imatinib-resistant kinase domain mutations are the major cause of relapse during imatinib therapy and the subsequent development of new inhibitors to treat CML patients. The development of imatinib validates an emerging paradigm in cancer, in which a tumor is defined by genetic abnormalities and effective therapies are developed that target events critical to the growth and survival of a specific tumor.
Authors
Daniel W. Sherbenou, Brian J. Druker
Abstract
There is widespread aberrant expression of mature and/or precursor microRNAs in cancer cells, as microRNAs are deregulated consequent to chromosomal alterations and other genomic abnormalities. The identification of such abnormalities has a clear diagnostic and prognostic significance, and there are ever increasing examples of links between certain human cancers and modifications at microRNA loci.
Authors
George A. Calin, Carlo M. Croce
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