Hematology/Oncology Clinics of North America RSS feed: Current Issue. Hematology/Oncology Clinics of North America updates you on the latest trends in patient management; keeps you up to date on the newest advances; and provides a sound basis for choosing treatment options. Each issue focuses on a single topic in hematogy and oncology and is presented under the direction of an experienced guest editor. http://www.hemonc.theclinics.com/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Hematology/Oncology Clinics of North America0889-8588263June 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.hemonc.theclinics.com/article/PIIS0889858812000524/abstract?rss=yesContributors10.1016/S0889-8588(12)00052-4Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6iiivhttp://www.hemonc.theclinics.com/article/PIIS0889858812000536/abstract?rss=yesContents10.1016/S0889-8588(12)00053-6Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6viiixhttp://www.hemonc.theclinics.com/article/PIIS0889858812000548/abstract?rss=yesForthcoming Issues10.1016/S0889-8588(12)00054-8Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6xxhttp://www.hemonc.theclinics.com/article/PIIS0889858812000470/abstract?rss=yesHosting as editor this 2012 issue of Hematology Oncology Clinics of North America is an opportunity to reflect on trends in clinical drug development. In particular, awareness of the incredible possibilities that our “new biology” conveys should not preclude continuing exploitation of “conventional” chemotherapy.Clinical Drug Development in 2012Franco Muggia10.1016/j.hoc.2012.03.003Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6xixiihttp://www.hemonc.theclinics.com/article/PIIS0889858812000238/abstract?rss=yesAntibody-based therapeutics against cancer are highly successful and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States. Bevacizumab, rituximab, and trastuzumab had sales in 2010 of more than $5 billion each. Hundreds of mAbs, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small-molecule drugs, and mAbs with optimized pharmacokinetics, are in clinical trials. However, deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems, and individual variations.Therapeutic Antibodies Against CancerMark J. Adler, Dimiter S. Dimitrov10.1016/j.hoc.2012.02.013Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6447481http://www.hemonc.theclinics.com/article/PIIS088985881200024X/abstract?rss=yesMammalian target of rapamycin (mTOR) is a serine/threonine protein kinase. It is ubiquitously expressed in cells and is a therapeutic target for the cancer treatment arsenal. Despite the great responses obtained in tumors addicted to specific mutations or overactivation of key members of the mTOR pathway (HiF1α in RCC, cyclin D1 in MCL, or TSC in SEGA), mTOR inhibitors as single agents have modest activity. Dual PI3K/mTOR kinase inhibitors have been developed with the idea of overcoming resistance to the mTOR inhibition through preventing the activation of PI3K/Akt as a result of release negative feedback loops.mTOR Signaling Pathway and mTOR Inhibitors in Cancer TherapyAlejandro Gomez-Pinillos, Anna C. Ferrari10.1016/j.hoc.2012.02.014Hematology/Oncology Clinics of North America 26, 3 (2012)2012-04-05Hematology/Oncology Clinics of North America2012-04-05263S0889-8588(11)X0009-6483505http://www.hemonc.theclinics.com/article/PIIS0889858812000263/abstract?rss=yesTopoisomerase 1 inhibitors cure human cancer xenografts in animal models, more so than most other chemotherapy agents. However, their activity in patients with cancer is modest. Ongoing research is studying the optimal analogues that could reproduce animal data in the cancer population. This article analyzes the clinical research with topoisomerase 1 inhibitors in ovarian cancer.Topoisomerase 1 Inhibitors and Cancer TherapyJulia Moukharskaya, Claire Verschraegen10.1016/j.hoc.2012.03.002Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6507525http://www.hemonc.theclinics.com/article/PIIS0889858812000056/abstract?rss=yesThe IGF axis is a tightly controlled endocrine system that regulates cell growth and development, known to have an important function in cancer biology. IGF1 and IGF2 can promote cancer growth in a GH-independent manner both through paracrine and autocrine secretion and can also confer resistance to chemotherapy and radiation. Many alterations of this system have been found in neoplasias, including increased expression of ligands and receptors, loss of heterozygosity of the IGF2 locus and increased IGF1R gene copy number. The IGF1 network is an attractive candidate for targeted therapy, including receptor blockade with monoclonal antibodies and small molecule inhibitors of receptor downstream signaling. This article reviews the role of the IGF axis in the initiation and progression of cancer, and describes the recent advances in IGF inhibition as a therapeutic tool.Targeting the Insulin Growth Factor Receptor 1Fernanda I. Arnaldez, Lee J. Helman10.1016/j.hoc.2012.01.004Hematology/Oncology Clinics of North America 26, 3 (2012)2012-02-29Hematology/Oncology Clinics of North America2012-02-29263S0889-8588(11)X0009-6527542http://www.hemonc.theclinics.com/article/PIIS088985881200010X/abstract?rss=yesGynecologic malignancies carry an estimated incidence of 83,750 cases per year and estimated mortality rate of more than 27,000 women per year. New therapies and therapeutic approaches are needed to improve the outlook for women with gynecologic cancers. Recent insights at the molecular and cellular levels are paving the way for a more directed approach to target mechanisms driving tumorigenesis. This article reviews the roles of new and emerging antiangiogenesis drugs, summarizes the data obtained from clinical trials of antiangiogenic agents, and discusses trials under way to address the role of such strategies in gynecologic cancers.Targeting Angiogenesis in Gynecologic CancersBehrouz Zand, Robert L. Coleman, Anil K. Sood10.1016/j.hoc.2012.01.009Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6543563http://www.hemonc.theclinics.com/article/PIIS0889858812000068/abstract?rss=yesThe Hedgehog (Hh) pathway is a signaling cascade that is evolutionally highly conserved and plays an important role in embryonic pattern formation and stem cell response to tissue damage. Given the pivotal role the Hh pathway plays in embryonic development in terms of proliferation and differentiation, it is not surprising that it has also been implicated in tumorigenesis and tumor growth acceleration in a vast variety of malignancies. This article summarizes the mechanism of Hh pathway signal transduction, discusses the models of pathway activation, reviews the clinical data using Hh inhibitors, and discusses challenges to the development of pathway inhibitors.Targeting the Hedgehog Pathway: Role in Cancer and Clinical Implications of Its InhibitionDeirdre J. Cohen10.1016/j.hoc.2012.01.005Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6565588http://www.hemonc.theclinics.com/article/PIIS0889858812000111/abstract?rss=yesIdentification of driver mutations in growth related protein kinases, especially tyrosine kinases, has led to clinical development of an array of tyrosine kinase inhibitors in various malignancies, including lung cancer. Improved understanding of tyrosine kinase biology has led to faster drug development, identification of resistance mechanisms, and ways to overcome resistance. This review discusses the clinical data supporting the use and practical aspects of management of patients on epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors.Tyrosine Kinase Inhibitors in Lung CancerAnish Thomas, Arun Rajan, Giuseppe Giaccone10.1016/j.hoc.2012.02.001Hematology/Oncology Clinics of North America 26, 3 (2012)2012-03-05Hematology/Oncology Clinics of North America2012-03-05263S0889-8588(11)X0009-6589605http://www.hemonc.theclinics.com/article/PIIS0889858812000081/abstract?rss=yesOf the agents available in the treatment of both solid and hematologic cancers, microtubule-targeted agents are among the most widely used and exploiting other mechanisms involving the microtubule and its role in mitosis is an area of continued interest. This review will focus on novel microtubule-targeted agents, both recently approved (eg, ixabepilone and eribulin) and in later-stage clinical trials, and kinase inhibitors that aim to directly inhibit the mitotic spindle, such as the aurora kinase, pololike kinase, and kinsein-spindle protein inhibitors.Antimitotic InhibitorsSusana M. Campos, Don S. Dizon10.1016/j.hoc.2012.01.007Hematology/Oncology Clinics of North America 26, 3 (2012)2012-03-26Hematology/Oncology Clinics of North America2012-03-26263S0889-8588(11)X0009-6607628http://www.hemonc.theclinics.com/article/PIIS0889858812000123/abstract?rss=yesThis article focuses on the cellular, biochemical, and molecular pharmacology of antifolates and how a basic understanding of the mechanism of action of methotrexate, its cytotoxic determinants, mechanisms of resistance, and transport into and out of cells has led to the development of a new generation of antifolates, a process that continues in the laboratory and in the clinics. New approaches to folate-based cancer chemotherapy are described based on the targeted delivery of drugs to malignant cells.The AntifolatesMichele Visentin, Rongbao Zhao, I. David Goldman10.1016/j.hoc.2012.02.002Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6629648http://www.hemonc.theclinics.com/article/PIIS0889858812000226/abstract?rss=yesRecently, the development of poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors as a synthetic lethality approach has brought a major breakthrough in the treatment of breast cancer susceptibility gene (BRCA)-mutant cancers. Because sporadic cancers have also been found to commonly have other defects in DNA repair, PARP inhibitors are under active clinical investigation in combination with DNA-damaging therapeutics in a wide range of sporadic cancers. In this review, the authors discuss DNA repair mechanisms and PARP as a therapeutic target and summarize an update on clinical trials of available PARP inhibitors and predictive biomarkers for their efficacy.Poly(Adenosine Diphosphate–Ribose) Polymerase Inhibitors in Cancer TreatmentSook Ryun Park, Alice Chen10.1016/j.hoc.2012.02.012Hematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6649670http://www.hemonc.theclinics.com/article/PIIS088985881200007X/abstract?rss=yesHistone deacetylase inhibitors (HDACI) have allowed pharmacologic manipulation of deregulated genes in cancer cells and have shown single-agent activity against T cell lymphomas, cutaneous T cell lymphomas, mantle cell lymphomas, and Hodgkin disease. The bigger promise of these agents is in enhancing the activity of other targeted therapies. In addition, the effects of HDACI on the immune system and cytokines indicate that HDACI can be useful in the treatment of immune dysfunction underlying tumorigenesis, autoimmune disorders, and graft-versus-host disease. There is also an effort to determine whether class specificity of HDACI has a biologic significance.Role of Histone Deacetylase Inhibitors in the Treatment of Lymphomas and Multiple MyelomaJasmine Zain10.1016/j.hoc.2012.01.006Hematology/Oncology Clinics of North America 26, 3 (2012)2012-03-29Hematology/Oncology Clinics of North America2012-03-29263S0889-8588(11)X0009-6671704http://www.hemonc.theclinics.com/article/PIIS088985881200055X/abstract?rss=yesIndex10.1016/S0889-8588(12)00055-XHematology/Oncology Clinics of North America 26, 3 (2012)2012-06-01Hematology/Oncology Clinics of North America2012-06-01263S0889-8588(11)X0009-6705714