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Identification and Treatment of Aggressive Thyroid Cancers (Part 2)In part 2, we address risk assessment and staging, findings that suggest the presence of aggressive tumors, recurrent/metastatic disease, and treatment with chemotherapy and external-beam radiotherapy. Experimental treatments utilizing molecular targets, redifferentiation agents, and gene therapy are covered briefly as well.
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Treatment of Aggressive Non-Hodgkin’s Lymphoma: A North American PerspectiveThe most common subtype of aggressive non-Hodgkin’s lymphomais diffuse large B-cell lymphoma (DLBCL). Diffuse large B-cell lymphomarepresents a heterogeneous entity, with 5-year overall survivalrates ranging from 26% to 73%. Microarray gene expression studieshave confirmed that biologically distinct subgroups exist within DLBCL,and can be correlated with outcome. Initial management is usuallyguided by stage of disease at presentation. Approximately 25% of patientswith DLBCL present with limited-stage disease and are treatedwith combined-modality therapy (brief chemotherapy and involved-fieldradiation). Most patients present with advanced-stage disease and requiretreatment with an extended course of chemotherapy. The CHOP(cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone)chemotherapy regimen has been the mainstay of therapy sinceits development in the 1970s, as more intensive chemotherapy regimensfailed to show additional benefit. The era of monoclonal antibodieshas transformed treatment practices for aggressive lymphoma andhas led to a significant improvement in outcome. A randomized trialcomparing the use of rituximab (Rituxan), a chimeric anti-CD20 IgG1monoclonal antibody, combined with CHOP chemotherapy vs CHOPchemotherapy alone for elderly patients with advanced-stage DLBCLdemonstrated a significant benefit for the combination approach. Thisfinding has now been confirmed in two additional randomized, controlledtrials and a population-based analysis, making CHOP andrituximab the standard of care for all newly diagnosed patients withDLBCL. Despite this advance, newer therapies are needed and manyare under active investigation. The insights gained from molecular techniquessuch as gene expression profiling should permit identificationof additional lymphoma-specific therapeutic targets and the developmentof novel agents that take into account underlying biology andallow for greater tailoring of therapy.
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New Directions in the Treatment of Advanced Colorectal CancerAs the chemotherapy horizons have expanded in colorectal cancer with development of oxaliplatin (Eloxatin) and irinotecan (CPT-11, Camptosar), so too have our approaches to therapy. Numerous immunotherapy and gene
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
Latest:
The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
Latest:
The Promise of Pharmacogenomics: Gemcitabine and PemetrexedAlthough no overall differences in survival have been observed betweenthe many chemotherapy combinations in non–small-cell lungcancer, the clinical application of mRNA expression levels of amplifiedgenes may disclose many genetic influences on cytotoxic drug sensitivityand enable clinicians to tailor chemotherapy according to eachindividual’s gene profile. Specifically, the assessment of ribonucleotidereductase subunit M1 and thymidylate synthase mRNA expression levelsmight select patients who benefit from gemcitabine (Gemzar) orpemetrexed (Alimta) combinations. Until recently, clinical prognosticfactors such as performance status, weight loss, and lactate dehydrogenasewere the only parameters used to predict chemotherapy responseand survival. However, accumulated data indicate that overexpressionof genes involved in cancer glycolysis pathways plays an important role,and might be an independent mechanism of chemoresistance. Thedysregulation of glycolytic genes is affected by growth signals involvingthe PI3K/Akt pathway and downstream genes such as hypoxiainduciblefactor-1-alpha. One can thus envision that substantial improvementsin therapeutic outcome could benefit from the integrationof tailored ribonucleotide reductase-dependent chemotherapy, ribonucleotidereductase antisense therapy, and targeted therapy.
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Investigating CAR T-Cell Signals May Lead to New ApproachesRecent studies on CAR T-cell immunotherapy, and the recent approval of a new agent, add to evidence supporting the efficacy of these therapies.
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Gene Editing Leads to Successful Outcome for Pediatric ALL PatientWaseem Qasim, MBBS, PhD, and his team began researching a novel strategy to enable “off-the-shelf”’ therapy with mismatched donor chimeric antigen receptor (CAR)19 T cells.
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Bristol Myers Squibb Withdraws Nivolumab Indication for Treatment of SCLCNivolumab was previously granted accelerated approval by the FDA for the treatment of patients with small cell lung cancer (SCLC) whose disease had progressed after platinum-based chemotherapy and at least 1 other line of therapy, but phase 3 trial results led to a decision to withdraw the indication.
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The Promise of Chimeric Antigen Receptor T-Cell TherapyIn this review, we will describe the mechanism of action of CAR T cells, discuss outcomes of current clinical trials, and highlight emerging directions for this exciting approach to cancer treatment.
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Progress With Cross-Disciplinary Collaboration in Cell Therapy for Autoimmune DiseaseDavid Porter, MD, the director of cell therapy and transplant at Penn Medicine, also summed up his main message regarding the current state of the field in general.
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FDA Approves Brentuximab Vedotin for Cutaneous LymphomaThe FDA has approved brentuximab vedotin (Adcetris) for the treatment of primary cutaneous anaplastic large-cell lymphoma and CD30-expressing mycosis fungoides in patients who have received prior systemic therapy.
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CAR T-Cell Therapy in ALL: Formidible Challenges RemainAt the NCCN Annual Conference, Dr. Bijal Shah of Tampa’s Moffitt Cancer Center highlighted ongoing challenges in administration of CAR T-cell therapy.
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Managing CAR T-Cell Therapy in Patients With Hematologic MalignanciesStephanie Jackson, MSN, RN speaks with Cancer Network about the role oncology nurses play in managing patients with hematologic malignancies who are undergoing CAR T-cell therapy.
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CAR T-Cell Therapy in Non-Hodgkin Lymphoma PatientsDr. Copelan discusses the use of chimeric antigen receptor (CAR) T-cell therapy in non-Hodgkin lymphoma patients and how these therapies might improve upon the current standard of care.
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Managing Cytokine Release Syndrome in Patients on CAR T-Cell TherapyAhead of the ASCO Annual Meeting, we discuss the assessment and management of cytokine release syndrome in patients with cancer with Elizabeth Shpall, MD.
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Pediatric Acute Lymphoblastic LeukemiaONCOLOGY discussed therapy options, including chimeric antigen receptor (CAR)-T-cell therapies for pediatric acute lymphoblastic leukemia (ALL), with Susan R. Rheingold, MD, Medical Director of the Oncology Outpatient Clinic and attending physician with the Cancer Center at Children’s Hospital of Philadelphia.
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Dylan Essner on Documentation Tools for CAR T-Cell TherapyDylan Essner discussed the implementation of documentation tools and CRS, ICANS and ICE flow sheets within CAR T-cell therapy.
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Stem Cell Therapy Studies in TBI and Stroke: Bijan Nejadnik, MDThe chief medical officer at SanBio discussed how the investigational agent SB623 is being studied in TBI and stroke, with future planned studies in Alzheimer disease.
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Stem Cell vs Gene Therapy Processes in Sickle Cell DiseaseA discussion of the course of gene therapy compared with stem cell therapy.
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Making Noise About "Silent" Mutations in Treating Skin CancerMelanoma and other types of skin cancer are among the many types of cancer poised to benefit greatly from genomic research that identifies susceptibilities and potential targets for genetic-based therapy. A recent paper in Pigment Cell & Melanoma Research suggests, however, that an entire category of genetic mutations – one that could be incredibly fruitful in terms of diagnosis and treatment – is largely being ignored.
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Stem Cell Therapy for Myasthenia GravisRefractory cases of myasthenia gravis can be relieved by a new treatment based on replacing a patient’s immune system with new one created from transplants of his own stem cells, Canadian researchers report.
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New Stem Cell Therapy May Treat Crohn's DiseaseStem cell transplants may be a new, revolutionary way to treat Crohn's disease.
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Stem Cell Therapy Could Stop MS for Many Years, But Funding is an IssueExperimental stem cell therapy using a patient's own stem cells could offer long-term relief for many patients with multiple sclerosis, though questions still remain regarding cost, patient selection, and efficacy.
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Growth Hormone Therapy Effective at Increasing Anemics' Height During ChildhoodFor children with Diamond-Blackfan Anemia (DBA) - an inherited condition defined by low red blood cell counts and limited progenitor cells in the bone marrow - growth hormone (GH) therapy was found to increase the short stature of patients - a symptom not widely analyzed.
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The Virtual Window: Clinical Trial Reports--April 2007The Clinical Trials reported in this issue include: PHASE I: 1) Cell Genesys and Medarex Remain Positive on Combination Immunotherapy Study 2) Active Biotech Achieves Success with TASQ for Prostate Cancer PHASE II: 1) Myriad Initiates Evaluation of Brain Cancer Drug that Crosses the Blood-Brain Barrier 2) Second Lung Cancer Trial Adds Data to Novel Therapy PHASE III: 1) Nexavar Could Soon Add Primary Liver Cancer to its Label 2) Point Therapeutics Provides Clinical Update for NSCLC Studies
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Jakob Dupont, MD, on ATA188’s Potential in All Forms of Multiple SclerosisThe global head of research and development at Atara Biotherapeutics discussed ATA188 ahead of anticipated data readouts this month.
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Shai Efrati, MD: Inducing Stem Cell Proliferation With Hyperbaric Oxygen TherapyThe director of the Sagol Center for Hyperbaric Medicine and Research at Yitzhak Shamir Medical Center discussed how hyperbaric oxygen therapy is being used to attempt to improve the damage from neurodegeneration.
