Cancer therapy. New strategies and treatment modalities for optimizing patient outcomes.
In the postgenome era, development of novel targeted therapeutics is anticipated to accelerate, with the promise of specifically tailored strategies to treat specific molecularly characterized disease entities. Greater understanding of disease pathophysiology and pharmacologic actions at the molecular, cellular, and tissue levels have provided the basis for expanding the clinical application of available therapies such as recombinant human erythropoietin (r-HuEPO, epoetin alfa). The role of epoetin alfa in anemic cancer patients receiving chemotherapy has grown as our understanding of the relationship between anemia and quality of life in this patient population has evolved. With anemia and tumor hypoxia associated with poorer outcomes in various solid tumors, the potential impact of epoetin alfa on outcomes, as well as quality of life, in patients undergoing radiation or chemoradiation is of considerable interest. Anemia occurs almost universally in critically ill patients, resulting in substantial transfusion requirements. In this setting, the anemia appears to be consistent with anemia of chronic inflammatory disease and is potentially treatable by epoetin alfa. Recent preclinical studies indicate that erythropoietin exhibits neuroprotective effects in models of central nervous system injury, suggesting additional potential novel clinical applications for epoetin alfa worthy of careful investigation. Advances in the understanding of the ras genes and their functional proteins in signaling pathways involved in the development of cancer, particularly hematologic malignancies, over the last decade have prompted development of a new class of agents, farnesyl protein transferase inhibitors (FTIs), designed specifically to inhibit the initial step in Ras protein activation. Initial clinical evaluation of FTIs is ongoing, and preliminary results demonstrate antitumor activity in hematologic malignancies. Further identification and understanding of the function and complex interactions of proteins involved in diseases holds the promise of targeted therapies and improved patient outcomes.
Gabrilove
J L
JL
Division of Medical Oncology, Department of Medicine, The Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use; D051231:Farnesyltranstransferase; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015363:Quinolones / Q000627:therapeutic use; D011994:Recombinant Proteins
D004791:Enzyme Inhibitors; D015363:Quinolones; D011994:Recombinant Proteins; D004921:Erythropoietin; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; C402769:tipifarnib