As 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
Although 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.
Although 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.
Although 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.
Although 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.
Recent studies on CAR T-cell immunotherapy, and the recent approval of a new agent, add to evidence supporting the efficacy of these therapies.
Waseem 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.
Nivolumab 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.
In 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.
David 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.
The 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.
At the NCCN Annual Conference, Dr. Bijal Shah of Tampa’s Moffitt Cancer Center highlighted ongoing challenges in administration of CAR T-cell therapy.
Stephanie 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.
Dr. 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.
Ahead of the ASCO Annual Meeting, we discuss the assessment and management of cytokine release syndrome in patients with cancer with Elizabeth Shpall, MD.
ONCOLOGY 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.
Dylan Essner discussed the implementation of documentation tools and CRS, ICANS and ICE flow sheets within CAR T-cell therapy.
The 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.
A discussion of the course of gene therapy compared with stem cell therapy.
Melanoma 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.
Refractory 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.
Stem cell transplants may be a new, revolutionary way to treat Crohn's disease.
Experimental 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.
For 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.
The 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
The global head of research and development at Atara Biotherapeutics discussed ATA188 ahead of anticipated data readouts this month.
The 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.
Phase 2 trial results suggest the possibility of a treatment that may regenerate brain cells following TBI.
Spyridoula Vasileiou, PhD, discusses the potential role of ALVR109, a SARS-CoV-2 virus–specific T-cell therapy, for the treatment of coronavirus disease 2019.