Livestrong Foundation

About: Livestrong Foundation is a nonprofit organization based out in Austin, Texas, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 70 authors who have published 231 publications receiving 16662 citations. The organization is also known as: Lance Armstrong Foundation.

Patient-derived tumour xenografts as models for oncology drug development

Abstract: Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.

Phase I and Pharmacologic Study of OSI-774, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced Solid Malignancies

Abstract: PURPOSE: To assess the feasibility of administering OSI-774, to recommend a dose on a protracted, continuous daily schedule, to characterize its pharmacokinetic behavior, and to acquire preliminary evidence of anticancer activity PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of OSI-774 in three study parts (A to C) to evaluate progressively longer treatment intervals Part A patients received OSI-774 25 to 100 mg once daily, for 3 days each week, for 3 weeks every 4 weeks Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose (MTD) In part C, patients received this MTD on a continuous, uninterrupted schedule The pharmacokinetics of OSI-774 and its O-demethylated metabolite, OSI-420, were characterized RESULTS: Forty patients received a total of 123 28-day courses of OSI-774 No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in pa

Development of Matrix Metalloproteinase Inhibitors in Cancer Therapy

Abstract: The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of the extracellular matrix. The MMPs have been implicated in the processes of tumor growth, invasion, and metastasis; are frequently overexpressed in malignant tumors; and have been associated with an aggressive malignant phenotype and adverse prognosis in patients with cancer. A number of MMP inhibitors are being developed for the treatment of cancer. The most extensively studied class of MMP inhibitors includes collagen peptidomimetics and nonpeptidomimetic inhibitors of the MMP active site, tetracycline derivatives, and bisphosphonates. The hydroxamate peptidomimetic inhibitor batimastat and its orally bioavailable analogue marimastat, which bind covalently to the zinc atom at the MMP-active site, were the first MMP inhibitors to be studied in detail. Marimastat is currently being studied in randomized clinical trials. The nonpeptidic MMP inhibitors were synthesized in an attempt to improve the oral bioavailability and pharmaceutical properties of the peptidic inhibitors. Several members of this class of compounds are undergoing evaluation in phase III clinical trials. The tetracyclines and, particularly, the nonantibiotic chemically modified tetracyclines, interfere with several aspects of MMP expression and activation and inhibit tumor growth and metastases in preclinical models. A representative agent of this class, Col-3, is currently undergoing phase I clinical trials. The development of the MMP inhibitors, like that of other targeted and predominantly antiproliferative compounds, poses a challenge because the paradigms that have governed the design of clinical oncology trials may not be relevant to this new class of agents. The anticipated need for long-term administration of these drugs, together with their cytostatic mechanism of action, will require novel clinical trial design strategies.

Clinical Applications of Metabolomics in Oncology: A Review

Abstract: Metabolomics, an omic science in systems biology, is the global quantitative assessment of endogenous metabolites within a biological system. Either individually or grouped as a metabolomic profile, detection of metabolites is carried out in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry. There is potential for the metabolome to have a multitude of uses in oncology, including the early detection and diagnosis of cancer and as both a predictive and pharmacodynamic marker of drug effect. Despite this, there is lack of knowledge in the oncology community regarding metabolomics and confusion about its methodologic processes, technical challenges, and clinical applications. Metabolomics, when used as a translational research tool, can provide a link between the laboratory and clinic, particularly because metabolic and molecular imaging technologies, such as positron emission tomography and magnetic resonance spectroscopic imaging, enable the discrimination of metabolic markers noninvasively in vivo. Here, we review the current and potential applications of metabolomics, focusing on its use as a biomarker for cancer diagnosis, prognosis, and therapeutic evaluation.