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Showing 5851 - 5900Neoadjuvant Aromatase Inhibitor Therapy Converts Many Patients to Candidates for Breast-conserving Surgery
The American College of Surgeons Oncology Group (ACOSOG) Z1031 trial examined the effect of neoadjuvant aromatase inhibitor therapy on clinical response and breast-conservation rates in postmenopausal women with estrogen receptor (ER)-rich stage II or III breast cancer. An update of the surgical...
Using Imatinib for Adjuvant Treatment after Resection of Kit (CD117)-positive Gastrointestinal Stromal Tumors
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In January 2012, imatinib mesylate (Gleevec) was granted ...
SMAC Mimetics Induce Proinflammatory Cancer Cell Death and Adaptive Antitumor Immune Response
SMAC/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI) is a proapoptotic mitochondrial protein that is released in response to various apoptotic stimuli. Molecular mimetics of SMAC are being investigated for use in cancer treatment,...
Bone Morphogenesis Protein 4 Pathway as Treatment Target in Hepatocellular Carcinoma
Bone morphogenesis protein 4 (BMP4), which belongs to the transforming growth factor (TGF)-β family, is a multifunctional cytokine that is known to be involved in human carcinogenesis. The cytokine exerts its effects through pathways dependent on and independent of SMAD proteins, which are the...
Targeting Human Endogenous Retrovirus K Envelope Protein Inhibits Breast Cancer Growth
The human genome contains a large variety of endogenous retroviral sequences (approximately 8% of the genome). Although most of these are highly defective, the human endogenous retrovirus type K (HERV-K) family shows conservation of apparently intact retroviral genes and is transcriptionally active ...
PEDF Has Cytotoxic Effect on Breast Cancer Cells and Neuron-protective Effect
The cytokine pigment epithelium–derived factor (PEDF) is downregulated in brain metastases of breast cancer by approximately 14-fold compared with primary breast tumors, suggesting that promoting its expression might inhibit metastatic spread. Normal breast epithelial cells express high levels of...
Inhibition of IL-8 Receptor Reduces Colorectal Cancer Proliferation and Sensitizes the Disease to Oxaliplatin
Recent studies have shown that interleukin-8 (IL-8) and its receptors CXCR1 and CXCR2 are significantly upregulated in colorectal cancer tumors and their microenvironment and act as regulators of proliferation, angiogenesis, and metastasis. Ning and colleagues from the University of Southern...
Characteristics of Field Cancerization in Histologically Normal Tissue Adjacent to Breast Tumors
It has been shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The characteristics of this field are not fully understood, although it is clear that the molecular alterations in affected cells could provide...
Oral Rivaroxaban Is Noninferior to Standard Anticoagulant Therapy in Acute Pulmonary Embolism
Thromboembolic disease is common in patients with cancer and increases risk of mortality. Recent studies showed that the oral factor Xa inhibitor rivaroxaban (Xarelto) was as effective and safe as standard anticoagulant therapy in treating deep-vein thrombosis, with superior efficacy of rivaroxaban ...
Canadian Registry Study of Adjuvant Therapy for NSCLC Shows Increased Use in Elderly Patients and Improved Survival
Cisplatin-based adjuvant therapy is recommended for patients with resected stage II–IIIA non–small cell lung cancer (NSCLC). There have been no trials of adjuvant therapy in elderly patients with NSCLC, who constitute a large part of the NSCLC population. A number of analyses indicate that older...
Expert Point of View: Chemoradiation with Fluorouracil and Mitomycin Reduces Recurrence of Muscle-invasive Bladder Cancer
In an editorial accompanying the recently reported UK phase III Bladder Cancer 2001 (BC2001) trial, Shipley and Zietman, from Massachusetts General Hospital and Harvard Medical School, point out that this trial shows that “the addition of a very tolerable regimen of chemotherapy to radiotherapy...
Chemoradiation with Fluorouracil and Mitomycin Reduces Recurrence of Muscle-invasive Bladder Cancer
Radiotherapy is an alternative to surgery in muscle-invasive bladder cancer, particularly in less-fit patients. However, it is associated with high rates of incomplete response or recurrence, with salvage surgery often being required. Although synchronous chemoradiotherapy has improved local...
Vandetanib: New Drug for Unresectable Medullary Thyroid Cancer
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication The oral kinase inhibitor vandetanib (Caprelsa) was...
Study Shows Continued Benefit of PSA Screening in Reducing Prostate Cancer Mortality
Studies assessing the effect of prostate-specific antigen (PSA) testing on prostate cancer mortality have produced conflicting results, and recommendations regarding PSA screening vary among authorities. The recently published 11-year follow-up of the European Randomized Study of Screening for...
Inhibition of SFRP2 Found to Inhibit Growth of Triple-negative Breast Tumors
Secreted frizzled related protein 2 (SFRP2), a protein that modulates the Wnt signaling pathway and is involved in embryonic development, has been thought to exert a tumor-suppressive effect via inhibition of β-catenin activation. However, researchers at the University of North Carolina at Chapel...
Regional Infusion of Designer T Cells to Treat Intrahepatic Metastases
Designer T cells are modified from normal T cells to express specific immune receptors that allow them, via antibody-directed recognition or other mechanisms, to kill malignant cells bearing particular antigens. The Surgical Immunotherapy Lab at the Roger Williams Medical Center, Providence, Rhode...
Anti-EpCAM Antibody-Drug Conjugate Shows High Activity against Pancreatic Cancer
Human epithelial cell adhesion molecule (EpCAM) is overexpressed in many cancers. Although anti-EpCAM antibodies have shown promise in preclinical studies, early-phase clinical evaluation of these antibodies has been disappointing. To determine whether the antitumor activity of anti-EpCAM antibody...
Gab2 Promotes Characteristics of Epithelial-to-Mesenchymal Transition in Ovarian Cancer
Ovarian cancer is often diagnosed at a late stage, when cancer cells have already migrated and invaded other tissues and organs. Wang and colleagues from the University of Colorado Denver and the Dana-Farber Cancer Institute in Boston, showed that Gab2—a scaffolding adaptor protein that is...
Complex Relationship between Metformin and BRAF-mutant Tumors
The antidiabetic drug metformin appears to lower cancer risk in diabetic patients and has shown antitumor activity in preclinical studies. Suppression of mTOR signaling via AMP kinase (AMPK)-dependent TOR complex 1 (TORC1) inhibition is one of the proposed mechanisms by which metformin appears to...
Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer
Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess...
What You Need to Know About Glucarpidase Injection for Toxic Methotrexate Levels in Renal Impairment
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In January 2012, glucarpidase injection (Voraxaze) was...
Newest Indication for Rituximab as Maintenance Treatment in Non‑Hodgkin Lymphoma
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication The CD20-directed monoclonal antibody rituximab...
Everolimus: New Indication in Renal Angiomyolipoma Associated with Tuberous Sclerosis Complex
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In April 2012, the kinase inhibitor everolimus...
Multicenter Phase II Trial Supporting Approval of Brentuximab Vedotin in Anaplastic Large-cell Lymphoma
Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive T-cell lymphoma subtype characterized by uniform expression of CD30. Apart from low- to intermediate-risk patients with ALK-positive disease, patients with ALCL have a poor prognosis when treated with conventional, anthracycline-based...
Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer
Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess...
Pazopanib: New Drug for Advanced Soft-tissue Sarcoma
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In April 2012, pazopanib (Votrient) was approved for the ...
Identification of Novel Mechanism for Suppression of Antitumor Immunity
The efficacy of cancer immunotherapy has been limited, likely reflecting in large part the incomplete understanding of the complex interactions between tumors and the immune microenvironment. A study presented at the 2012 ASCO Annual Meeting helps clarify some of these interactions. Changes in...
Early Access to Palliative/Supportive Care vs Usual Care Improves Pain Management
Many cancer patients remain undertreated for pain despite availability of guidelines and educational efforts to improve pain treatment. In a recent Annals of Oncology article, Bandieri and colleagues from the Italian Epidemiologia Clinico-Assistenziale del Dolore in Ospedale (ECAD-O) group report a ...
p53 Mutation in Advanced Solid Tumors Linked to Aggressive Course
Mutations in the tumor-suppressor protein p53, among the most common mutations in cancers, affect apoptosis, genomic stability, and angiogenesis. To determine the effect of p53 mutation on clinical characteristics and disease and treatment outcomes, Rabih Said, MD, MPH, and colleagues from The...
NK Cell Signature Associated with Favorable Prognosis in Breast Cancer
Tumor cell recognition by natural killer (NK) cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the tumor cells. NK cells also express adhesion molecules that facilitate formation of the immune synapse with tumor targets. Maria Libera...
Single Nucleotide Polymorphisms Predict Severe Toxicity of Adjuvant Therapy in Colorectal Cancer
Oxaliplatin/fluoropyrimidine–based adjuvant therapy is of benefit in patients with resected stage II/III colon cancer, but the ability to predict risk of toxicity could improve care by permitting individualization of treatment. Ana Custodio, MD, and colleagues from GEMCAD (Grupo Español...
Two Single Nucleotide Polymorphisms Associated with Risk for Paclitaxel-related Peripheral Neuropathy
Peripheral neuropathy is the most common severe toxicity in patients receiving paclitaxel, and mutations in genes affecting drug metabolism, distribution, and elimination are likely to modulate risk for such neurotoxicity. In a recent study, Daniel Hertz, PharmD, and colleagues from the University...
Alterations in PTEN Insufficient to Predict Sensitivity to Drugs Targeting PI3K/mTOR Pathway
PTEN acts as a tumor-suppressor gene through the action of its phosphatase protein product, which participates in regulation of the cell cycle to prevent too-rapid cell growth and division. Loss of PTEN function has been shown to increase PI3K/mTOR signaling, and preclinical data suggest that PTEN...
SIDEBAR: Key Findings
When asked to comment on implications of this study, lead author Frank A. Greco, MD, remarked, “The use of this gene-expression profile assay (CancerTYPE ID, bioTheranostics, Inc) on the biopsy material of patients with carcinoma of unknown primary provides a single tissue of origin diagnosis in...
Gene Profiling–guided Therapy May Improve Survival in Patients with Carcinoma of Unknown Primary
Molecular gene-expression profiling is an emerging technique to determine tissue of origin in patients with carcinoma of unknown primary, although the value of predictions from such profiling in improving treatment outcomes is unclear. In a prospective trial using tumor profiling results to direct...
Prognostic Value of Integrated Cytogenetic and Mutational Risk Classification in Acute Myeloid Leukemia
Jay P. Patel, BS, and colleagues from Memorial Sloan-Kettering Cancer Center in New York recently performed mutational analysis of 18 genes in a subgroup of newly diagnosed acute myeloid leukemia (AML) patients who had been randomized to receive cytarabine plus high-dose or standard-dose...
Increased Adjuvant Therapy Use and Improved Survival in Dutch Elderly Patients with Stage III Colon Cancer: A Direct Correlation?
A survival benefit of adjuvant chemotherapy has been reported for select elderly patients with stage III colon cancer, but many elderly patients are not candidates for or are not given adjuvant therapy due to comorbidities and fear of toxicity. In a recent Annals of Oncology article, van...
Pertuzumab: New Drug for HER2-positive Metastatic Breast Cancer
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In June 2012, pertuzumab (Perjeta) was approved for use...
No Improvement in Overall Survival, Worse Toxicity with Motesanib Added to Chemotherapy in Non–Small Cell Lung Cancer
Two trials (E4599 and AVAiL) have suggested a benefit to adding the anti–vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to chemotherapy in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). Bevacizumab acts by binding directly to circulating...
Radiotracer Targeting of Free Prostate-specific Antigen
Serum levels of prostate-specific antigen (PSA) are widely used as a biomarker for prostate cancer, although they often do not distinguish between normal tissue and cancer and do not always accurately reflect clinical outcome. In order to overcome the fact that the small proportion of...
Expert Point of View: James O. Armitage, MD
In an accompanying editorial entitled “Who Benefits From Surveillance Imaging?” James O. Armitage, MD, University of Nebraska Medical Center, Omaha, noted that data on surveillance imaging (CT or PET/CT) indicate a general absence of survival benefit in adults with lymphomas, while pointing out...
Study Shows Routine CT Surveillance Overused in Pediatric Hodgkin Lymphoma
The value of routine CT surveillance monitoring of pediatric patients for recurrence of Hodgkin lymphoma has been unclear. A study of CT surveillance recently reported by Stephan D. Voss, MD, PhD, and colleagues from the Children’s Oncology Group (COG) in the Journal of Clinical Oncology showed...
Carfilzomib: New Drug with Accelerated Approval for Multiple Myeloma
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In July 2012, carfilzomib (Kyprolis) was granted...
No Advantage to Longer Adjuvant Chemotherapy in Women with Early Breast Cancer: CALGB 40101 Trial
The ideal duration of adjuvant therapy for women with lower-risk primary breast cancer remains unknown. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-15 trial, reported more than 20 years ago, found no difference in outcomes between six cycles of cyclophosphamide, methotrexate,...
Ziv-aflibercept with FOLFIRI in Metastatic Colorectal Cancer
In August 2012, the antiangiogenic agent ziv-aflibercept (Zaltrap) was approved for use in combination with FOLFIRI (fluorouracil, leucovorin, irinotecan) for the treatment of metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen.1,2 Approval was based on...
New Indication for Cetuximab plus FOLFIRI to Treat EGFR-positive, Wild-type KRAS Metastatic Colorectal Cancer
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In July 2012, cetuximab (Erbitux) was approved for use...
TRIM27 as Target in Cancer Development
The tripartite motif family protein 27 (TRIM27) is a transcriptional repressor that reduces induction of cell senescence by retinoblastoma-associated protein (RB1). High levels of TRIM27 expression occur in several human cancers and have been associated with poor prognosis in breast and endometrial ...
VEGF Pathway Biomarker for Outcome with Bevacizumab
No biomarkers are available to guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab (Avastin). Lambrechts and colleagues from VIB and KULeuven and University Hospital Gasthuisberg, Belgium, and F. Hoffmann-La Roche in Basel, Switzerland, have identified a locus...
Evolutionary Pathways in BRCA1-associated Breast Tumors
BRCA1 germline mutations are associated with elevated risk of breast and ovarian cancers, and somatic loss of the wild-type BRCA1 allele has been thought to be a rate-limiting initiating step in tumor development. BRCA1-associated breast tumors acquire additional somatic alterations during...
Metastasis Promoted by Cleaving and Inhibiting Proapoptotic Effect of von Willebrand Factor
Mochizuki and colleagues from Keio University in Tokyo, the Chemo-Sero-Therapeutic Research Institute in Kumamoto, and RIKEN in Saitama have shown that von Willebrand factor has proapoptotic effects and that a disintegrin and metalloproteinase 28 (ADAM28) promotes metastasis by cleaving and...
