Lung Cancer: Translational and Emerging Therapies PDF

Preface

Lung cancer is the most common cancer worldwide, affecting over a million people every year, and it is the leading cause of death. Despite modest improvements in therapy, the five-year survival of this disease is less than 15%. The mainstay of treatment is surgery and adjuvant chemotherapy for early stage disease, concurrent chemoradiotherapy for locally advanced disease, and chemotherapy for metastatic disease. Molecularly targeted treatments are now coming to the fore, and epidermal growth factor receptor tyrosine kinase inhibitors such as erlotinib (Tarceva®) are now approved for use as second-line or third-line treatment of metastatic disease. Although not yet established as standard therapy, there are an ever increasing number of novel and targeted therapies being assessed in the treatment of lung cancer. These therapies are in varied stages of development and include antiangiogenesis inhibitors, epidermal growth factor receptor inhibitors, tumor vaccines, monoclonal antibodies, and endothelial receptor antagonists, to name just a few. Also in development are combination therapies of established treatments with targeted therapies. These emerging therapies reflect our expanding understanding of mechanisms of tumorogenesis and cell growth. This book provides the state-of-the-art information on evolving translational therapies in lung cancer. Currently, there is no text on this topic that assembles, reviews, and synthesizes this material in one volume.

It is appropriate that Drs. Gandara and Gummerlock and their colleagues set the stage and describe the molecular biology of lung cancer as the basis for targeted therapy in their chapter. Dr. Janet Dancey describes some of the more challenging aspects of clinical trial design issues related to clinical evaluation of these novel agents.

Some agents that have shown promise include angiogenesis inhibitors, antibody to vascular endothelial growth factor receptor, small molecule tyrosine kinase, and other multi-targeted agents. Drs. Ramnath and Adjei describe the basis of antiangiogenic therapy as well as provide a comprehensive review of small molecule inhibitors of angiogenesis, followed by a chapter on inhibition of angiogenesis using monoclonal antibodies by Drs. Dubey and Salgia. Drs. Jimeno and Hidalgo discuss the targeting of the epidermal growth factor receptor in the treatment of lung cancer, and Dr. Fred Hirsch and his colleagues discuss the markers of sensitivity and response to treatment with these agents. Drs. Papadopoulos and Tolcher complete the discussion with their chapter on other novel targeted therapies, including such targets as Bcl, tumor necrosis factor–related apoptosis-inducing ligand receptors, inhibitor of apoptosis proteins family, and proteosome.

Vaccine therapy remains a promising area of research, and Dr. Davies and her colleagues update us on cancer immunology and the exciting data on several novel vaccine approaches and other new methods to modify the immune response.

Technological advances in the delivery of radiation as well as newer chemotherapeutic agents have produced improvements in combining these modalities for the treatment of locally advanced disease, as discussed by Drs. Milano and Chen, and also in the treatment of brain metastases, as discussed by Drs. Siker and Mehta. Technological advances in radiological imaging is making it possible to delineate the size and the location of tumors more precisely, as well as detect the presence of metastatic disease, allowing for more accurate staging of the disease as reviewed by Drs. Bhatt and Dogra.

Compared to a decade ago, we have made significant progress in understanding the molecular biology of lung cancer and the potential therapeutic targets in this disease, none of which would be possible without the untiring efforts of researchers and cooperation of the patients and their families.