Abstract:
:In the last decade our understanding of chronic lymphocytic leukemia (CLL) biology and pathogenesis has increased substantially. These insights have led to the development of several new agents with novel mechanisms of action prompting a change in therapeutic approaches from chemotherapy-based treatments to targeted therapies. Multiple preclinical models for drug development in CLL are available; however, with the advent of these targeted agents, it is becoming clear that not all models and surrogate readouts of efficacy are appropriate for all drugs. In this review we discuss in vitro and in vivo preclinical models, with a particular focus on the benefits and possible pitfalls of different model systems in the evaluation of novel therapeutics for the treatment of CLL.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Herman SE,Wiestner Adoi
10.1053/j.seminoncol.2016.02.007subject
Has Abstractpub_date
2016-04-01 00:00:00pages
222-32issue
2eissn
0093-7754issn
1532-8708pii
S0093-7754(16)00013-0journal_volume
43pub_type
杂志文章,评审abstract::Solid malignancies often exhibit high interstitial fluid pressure (IFP), which causes poor uptake of anticancer drugs. While there are several mechanisms that regulate IFP in tumors, activation of platelet-derived growth factor receptor, which is expressed in various cell types within the tumor microenvironment, has b...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.03.036
更新日期:2004-04-01 00:00:00
abstract::Small cell carcinoma (SCC) has become recognized as a distinct, though relatively infrequent, clinical pathology that occurs in multiple sites throughout the head and neck. Excluding cases that are considered to arise from skin, SCC in the head and neck has been found to develop in nearly all structures associated wit...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2006.10.024
更新日期:2007-02-01 00:00:00
abstract::A phase II study was performed to investigate the tolerance and efficacy of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and gemcitabine in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). To date, 24 patients (five with stage IIIB and 19 with stage IV NSCLC...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1997-08-01 00:00:00
abstract::Because studies of breast cancer patients and their relatives provide statistical evidence for involvement of autosomal dominant genes, the identification of specific genetic effects has long been the focus of efforts to identify women at exceedingly high risk. BRCA1, a gene that confers greatly increased susceptibili...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-02-01 00:00:00
abstract::In order to correlate changes in morphology to changes in molecular attributes, we constructed a tissue microarray of thin and thick melanomas selected to represent progression from dysplasia to early and advanced melanoma. Hematoxylin and eosin (H&E) staining and immunohistology with antibodies to cyclin D1, p16, Ki6...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.09.014
更新日期:2007-12-01 00:00:00
abstract::The majority of patients with advanced prostatic cancer respond either to castration or estrogen therapy. In an attempt to identify an alternative hormonal therapy, 25 symptomatic stage D prostate cancer patients were treated with megestrol acetate as initial hormonal therapy. Thirty-three patients were evaluable for ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::In the United States there are approximately 100,000 women living with metastatic breast cancer. Bone is the most common site of breast cancer metastases and it is estimated that up to 85% of patients dying from this disease have developed osseous involvement. Skeletal metastases are often associated with dangerous an...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2001.25445
更新日期:2001-08-01 00:00:00
abstract::This phase I/II study was done to evaluate the safety and feasibility of two schedules of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 1-hour infusion in the outpatient setting. Fifty-six patients with advanced, refractory malignancies received one of two paclitaxel schedules by rand...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-10-01 00:00:00
abstract::Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious oste...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::The outcomes in young adults aged 20-39 with sarcoma tend to be inferior compared to those in children and adolescents. There are differences in sarcoma histotype distribution with age, such that pediatric-type tumors predominate in the 20- to 25-year-old group while more adult-type sarcomas occur in those aged 35-39 ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2009.03.006
更新日期:2009-06-01 00:00:00
abstract::Lung cancer represents the leading cause of cancer mortality worldwide. Its incidence has declined in men but is increasing in women, assuring that this largely preventable disease will continue to affect millions. In small cell lung cancer, the advent of chemotherapy in the 1970s and continued refinements in the 1980...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, often presenting with distant metastasis. While controversy exists regarding the actual incidence of the disease, there is agreement that IBC causes a disproportionate number of breast cancer deaths. Those with typical IBC symptoms face a h...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2007.11.011
更新日期:2008-02-01 00:00:00
abstract::Knowledge of the pharmacokinetics of a drug is essential to the optimal design of the dose and schedule of chemotherapy protocols. As an extension, an understanding of the mechanism of drug action is necessary to construct the optimal strategy for combination chemotherapy. Nucleoside antimetabolites such as fludarabin...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::Long-term survival is occasionally observed in patients with neoplastic meningitis (NM) accompanying breast cancer (13% one-year and 6% 2-year survival), melanoma, and lymphoma, but in general the survival of most patients is short and averages only 3 to 4 months. The incidence of NM appears to be increasing, in part ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2006.04.016
更新日期:2006-06-01 00:00:00
abstract::We report the updated results of an intensive treatment protocol for children (< 18 years) and adults (> or = 18 years) with advanced B-cell lymphomas. The protocol consists of two chemotherapy regimens: A, consisting of cyclophosphamide, doxorubicin, vincristine and high-dose methotrexate (CODOX-M), and B, consisting...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1998-04-01 00:00:00
abstract::The curative management of gastric adenocarcinoma depends on complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) impro...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(03)00298-7
更新日期:2003-08-01 00:00:00
abstract::Present status of gastric cancer surgery in Japan and several new procedures are reviewed in this article. Japanese treatment results of this disease were significantly better than Western results even when stages were adjusted. Generally speaking, Japanese surgical procedures are more aggressive and meticulous compar...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-06-01 00:00:00
abstract::The median latency of 2 degrees MDS/AL is 4 to 5 years. A high percentage of patients with 2 degrees MDS/AL convert to 2 degrees AL. Survival of either is less than 1 year. A constellation of morphologic abnormalities from all 3 cell lines produces a unique appearance. Both 2 degrees MDS and 2 degrees AL are difficult...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1992-02-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated substantial single-agent activity against both minimally pretreated and resistant metastatic breast cancer. Evaluation of paclitaxel-based combinations has demonstrated appreciable activity, but also toxicity, for the paclitaxel/doxorubic...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Almost 125 years after the first documented case, pulmonary metastasectomy is still poorly understood. No other organ is subject to the wide histologic variety of metastatic insults, and this fact has complicated a complete exposition of when pulmonary metastasectomy may be beneficial. Many physicians still consider p...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.03.004
更新日期:2007-06-01 00:00:00
abstract::Although chemotherapy for advanced bladder cancer has historically been based on cisplatin-based combination regimens, the limitations of these regimens both in terms of efficacy and toxicity are now widely appreciated. In response to these limitations, other single agents have been studied, and a number have demonstr...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-06-01 00:00:00
abstract::Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation of peripheral tolerance in order to prevent autoimmunity. Blocking of these cell surface proteins by antibodies has resulted in remarkable anti-tumor immunity; howev...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2015.02.011
更新日期:2015-06-01 00:00:00
abstract::The human tumor cloning system is an in vitro assay that has been used to predict response of patients' tumors to conventional antineoplastic agents as well as to biologic agents. In addition, the assay has been used to screen for antitumor activity of newly discovered cytotoxics and biologics. The purpose of the pres...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Among new patients with small cell lung cancer (SCLC), 20% to 25% are over 70 years of age and account for 8,000 cases annually in the United States. For such patients, intensive, aggressive, cytotoxic, combination chemotherapy is not often used because of its association with unacceptable morbidity and mortality rate...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::Immune dysregulation, a hallmark of chronic lymphocytic leukemia (CLL), manifests itself in three autoimmune diseases: warm autoimmune hemolytic anemia (AIHA); idiopathic thrombocytopenia (ITP); and, pure red cell aplasia (PRCA). AIHA occurs in 11% of advanced stage CLL patients. Prednisone is the first treatment of c...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-02-01 00:00:00
abstract::Previously untreated patients with stages I to IV, N0-3, M0 unresectable non-small cell lung cancer were randomized to arm I (conventional radiotherapy [RT], 60 Gy in 30 fractions over 6 weeks), arm II (accelerated RT, 60 Gy in 30 fractions over 3 weeks), arm III (conventional RT, as in arm I, plus carboplatin 70 mg/m...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-06-01 00:00:00
abstract::The effectiveness of current chemotherapeutic approaches for the treatment of solid tumors has reached a near plateau, suggesting we are nearing the limit of cytoreduction. It is hypothesized that this may be due to "subset effect," and that drugs administered according to responses predicted for particular subgroups ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1016/s0093-7754(01)90123-x
更新日期:2001-06-01 00:00:00
abstract::Alterations in chromatin structure resulting from aberrant DNA methylation and perturbations of the histone code profoundly influence gene expression during pulmonary carcinogenesis. Recent studies indicate that DNA demethylating agents and histone deacetylase (HDAC) inhibitors synergistically induce gene expression a...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.07.007
更新日期:2005-10-01 00:00:00
abstract::Constitutive expression of interferons (IFNs) and activation of their signaling pathways have pivotal roles in host responses to malignant cells in the tumor microenvironment. IFNs are induced by the innate immune system and in tumors through stimulation of Toll-like receptors (TLRs) and through other signaling pathwa...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.02.002
更新日期:2014-04-01 00:00:00
abstract::Interferon-alpha (IFN-alpha) therapy is frequently associated with significant fatigue, which is often the dominant dose-limiting side effect. The fatigue associated with IFN-alpha therapy is usually dose related, worsens with continued therapy, and is associated with significant depression. Although the direct cause ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-02-01 00:00:00