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BACKGROUND:Aggressiveness of inflammatory breast cancer (IBC) is related to its metastatic potential. The introduction of primary chemotherapy in the multimodality treatment has dramatically changed the prognosis. However, survival remains poor. Since 1995, innovative systemic therapies have been assessed in France in multicentric clinical trials, initially centered on high‐dose chemotherapy (HDC)...
Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal...
Many different targeted therapies with varying mechanisms of action have been added to standard first‐line chemotherapy doublets in an effort to improve survival of patients with advanced nonsmall cell lung cancer (NSCLC). Only 2 targeted therapies—bevacizumab and cetuximab—have been associated with superior survival in phase 3 first‐line studies. For both agents, the decision to enter phase 3 was...
BACKGROUND:Tumor vascularity is a potential predictor of treatment outcomes in metastatic renal cell carcinoma (mRCC), and contrast enhancement of tumors in computed tomography (CT) is correlated significantly with microvessel density. In this study, the authors investigated whether tumor enhancement in contrast‐enhanced CT (CECT) is useful for predicting outcomes in patients with mRCC who are receiving...
In the United States, randomized trials have established preoperative chemoradiation as the standard of care for patients with locally advanced rectal cancer. Pathologic complete response (pCR) rates occur in 10% to 16% of patients and have been shown to be correlated with both disease‐free and overall survival. Therefore, recent efforts incorporating newer cytotoxic and molecularly targeted agents...
BACKGROUND:Adult “translocation” renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)‐targeted therapy in this distinct subtype of RCC.
METHODS:A retrospective...
Cancers in children and adolescents are fortunately infrequent. Overall, cure rates are good, approximately 80%, although this varies by histology and stage. Targeted therapies aim to improve efficacy and decrease toxicity by more specifically affecting malignant cells or their supporting stroma. Cancers of early life are often of different histology than those seen in adults. Sometimes, the same...
BACKGROUND:Inhibitors of the mammalian target of rapamycin (mTOR) are emerging as promising therapies for metastatic renal cell carcinoma (RCC). Because rational treatment strategies require understanding the activation status of the underlying signaling pathway being targeted at the desired stage of disease, the authors examined the activation status of different components of the mTOR pathway in...
The focus of cancer research is on cancer‐specific mutations, with most clinical trials involving targeted drugs. Huge numbers of DNA lesions and tumor resistance events, in each of the >1013 cells of a human individual, form a striking contrast to the low, and also very narrow, cancer incidence window (10−1‐100). A detailed consideration of these quantitative observations seems to question the...
BACKGROUND.Chondrosarcoma (CS) is a rare and heterogeneous sarcoma in which, after failure of surgery and radiotherapy, chemotherapy plays only a marginal role. Different molecular pathways have been shown to be activated in CS; in particular, both isoforms of platelet‐derived growth factor receptor (PDGFR) are expressed and phosphorylated. These observations prompted investigation of the activity...
BACKGROUND:Although the presence of numerous cell signaling receptors in osteosarcoma is known, their simultaneous characterization has not been performed to date. The current study sought to characterize and quantify the expression of cell surface receptors across a variety of osteosarcoma cell lines.
METHODS:Standard (n = 4) and patient‐derived (n = 10) osteosarcoma cell lines were cultured and...
BACKGROUND:Simultaneous inhibition of the vascular epithelial growth factor (VEGF) and the mammalian target of rapamycin (mTOR) pathway may improve treatment response in advanced renal cell carcinoma (RCC). Everolimus, an oral mTOR inhibitor, and sunitinib, an oral tyrosine kinase inhibitor targeting VEGF, are standard agents in the management of metastatic RCC.
METHODS:Sequential cohorts of 3 to...
BACKGROUND:A wide range of hematologic malignancies arises from numerous cell types. In an attempt to offer a new target for treating B‐cell malignancies, in this study, the authors tested the possibility of using the CD40/CD40L system as a common targeting system for the various malignancies in this group.
METHODS:Two chimeric proteins, soluble CD40 ligand (sCD40L)‐caspase 3 (sCD40L‐l‐Caspase3)...
BACKGROUNDStudies have shown that skeletal muscle and adipose tissue are linked to overall survival (OS) and progression‐free survival (PFS). Because targeted therapies have improved the outcome in patients with metastatic renal cell carcinoma (mRCC), new prognostic parameters are required. The objective of the current study was to analyze whether body composition parameters play a prognostic role...
The widespread adoption of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the first‐line treatment of patients with advanced EGFR‐mutated non‐small cell lung cancer has resulted in acquired tyrosine kinase inhibitor resistance becoming a ubiquitous clinical problem. The identification of specific mechanisms of acquired resistance has allowed a better understanding of the biology...
Targeted therapy has emerged as an effective treatment option for certain molecular subsets of advanced stage non–small cell lung cancer (NSCLC). The discovery of the echinoderm microtubule‐associated protein like 4–anaplastic lymphoma kinase (EML4‐ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic. The first‐in‐class tyrosine...
Hepatocellular carcinoma is a common malignancy with a poor prognosis. Sorafenib is the only systemic therapy known to improve the overall survival of patients with advanced disease. The clinical benefit of sorafenib is modest and the mechanistic basis for its activity is unknown. Four phase 3 clinical trials have failed to improve on sorafenib in the frontline setting and no agent has been shown...
BACKGROUNDStandard biomarker testing of a single macroscopic disease site is unlikely to be sufficient because of tumor heterogeneity. A focus on examining global biomarker expression or activity, particularly in microscopic residual chemotherapy‐resistant disease, is needed for the appropriate selection of targeted therapies. This study was aimed at establishing a technique for the assessment of...
During the last decade, extensive multiplatform genome‐wide analysis has yielded a wealth of knowledge regarding the genetic and molecular makeup of glioblastoma multiforme (GBM). These profiling studies support the emerging view that GBM comprises a group of highly heterogeneous tumor types, each with its own distinct molecular and genetic signatures. This heterogeneity complicates the process of...
The discovery of “driver” genomic alterations in patients with non‐small cell lung cancer (NSCLC) has dramatically changed the field of thoracic oncology in recent years. The best understood of these molecular drivers are those involving the epidermal growth factor receptor (EGFR), which when aberrantly activated are integral to the development of a subset of NSCLC tumors. First‐generation and second‐generation...
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