Abstract:
:Modulation of the signaling pathways that are aberrant in cancer cells has the potential to provide an effective nontoxic approach to patient management in a broad range of cancers. This quest has taken a major leap forward with the demonstration that STI-571 (imatinib mesylate) induces clinical and molecular remissions in the majority of patients with interferon-refractory chronic myelogenous leukemia and gastrointestinal stromal tumors through inhibition of the Bcr/Abl fusion protein required for the initiation and progression of chronic myelogenous leukemia and inhibition of a mutant, activated c-kit present in gastrointestinal stromal tumors. Support for the concept of targeting products of fusion genes found in specific cancers was first provided by the efficacy of all-trans retinoic acid in acute promyelocytic leukemia where the RARalpha all-trans retinoic acid target is the target of multiple different chromosomal rearrangements. In breast cancer, trastuzumab, which alters the function of the HER2 proto-oncogene overexpressed in a portion of breast cancers, provides an additional example of targeting specific molecular aberrations present in cancer cells. Although the target for these signal transduction modulators is functional in normal cells, acceptable therapeutic indices sufficient to prevent tumor growth without unacceptable toxicities have been observed. Whether STI-571 and other signal transduction modulators also target the stroma, and specifically the neovasculature, in addition to the tumor remains an open question. The presence of the target in the cancer cells or in the surrounding stroma appears to be required but not sufficient for the action of molecular therapeutics. Thus, linking molecular diagnostics to identify patients where the target is amplified or activated and driving the pathophysiology of the patients' tumor to effective molecular therapeutics will be necessary to translate these concepts into approaches that will alter the outcome for breast cancer patients. This review will focus on the phosphatidylinositol 3-kinase pathway and novel molecules targeting this pathway to illustrate the questions and challenges underlying the implementation of molecular therapeutics in breast cancer.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Mills GB,Kohn E,Lu Y,Eder A,Fang X,Wang H,Bast RC,Gray J,Jaffe R,Hortobagyi Gdoi
10.1053/j.seminoncol.2003.08.011subject
Has Abstractpub_date
2003-10-01 00:00:00pages
93-104issue
5 Suppl 16eissn
0093-7754issn
1532-8708pii
S0093775403004445journal_volume
30pub_type
杂志文章,评审abstract::At present the only potentially curative treatment for hepatocellular carcinoma (HCC) is either partial hepatectomy or total hepatectomy with orthotopic liver transplantation (OLT). Underlying liver reserve and regenerative capacity are the most important determinants of the risk of postoperative hepatic failure after...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(01)90140-x
更新日期:2001-10-01 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::The treatment for patients with unknown primary carcinoma, particularly those with unfavorable prognosis factors, has changed in the last decade, and continues to evolve. Empiric chemotherapy trials reported since 2000 with the newer drugs have improved the overall survival compared to retrospective historical data an...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2008.10.005
更新日期:2009-02-01 00:00:00
abstract::Activation of mammalian target of rapamycin (mTOR) signaling occurs in a wide variety of human tumors and can lead to increased susceptibility to mTOR inhibitors. Temsirolimus, a novel analog of rapamycin, has shown promising preclinical and early clinical anti-tumor activity in various solid and hematologic tumor typ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2009.10.010
更新日期:2009-12-01 00:00:00
abstract::Recently, a randomized study conducted by the Gynecologic Oncology Group (GOG 111) demonstrated that, given by a 24-hour infusion, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is superior to combination cisplatin/cyclophosphamide in previously untreated patients with...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::Angiogenesis is required for multistage carcinogenesis. The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. COX-2 expression occurs in a wide range of preneoplastic and malignant conditions; and the enzyme has been localized to the neoplastic cells, endothelial cell...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.03.040
更新日期:2004-04-01 00:00:00
abstract::Advanced-stage mantle cell lymphoma (MCL) is a disease for which no curative treatment strategy exists. Results with standard combination chemotherapy, with or without an anthracycline, are disappointing, and new and better therapies are needed. High-dose therapy and autologous stem-cell transplantation (ASCT) have be...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:2002-02-01 00:00:00
abstract::Despite cures in early stage (IA-IIB) non-small cell lung cancer (NSCLC), the 5-year survival rate is only 36%-73%. Surgical resection via lobectomy is the treatment of choice in early-stage NSCLC, with the goal being complete anatomic resection of the tumor and mediastinal lymph node evaluation. Newer technologies, i...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2013.12.011
更新日期:2014-02-01 00:00:00
abstract::Choices of treatment for patients with estrogen receptor (ER) positive metastatic breast cancer refractory to first-line endocrine therapies include progestins, antiadrenal drugs, and androgens. These treatments should be administered sequentially to achieve maximum palliation of the disease. For ER positive patients ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1988-06-01 00:00:00
abstract::Most malignant melanomas in the ocular region arise in the uveal tract (iris, ciliary body, and choroid). Uveal melanoma generally has characteristic clinical features and the diagnosis can usually be made by an experienced ophthalmologist using slit lamp biomicroscopy or indirect ophthalmoscopy. Ancillary studies suc...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-12-01 00:00:00
abstract::For four decades, 5-fluorouracil was the only option available for patients with metastatic colorectal cancer. It provided a response rate of 15% to 20%, with a median survival of approximately 1 year. In the past 5 years, remarkable progress has been made in colorectal cancer research with the approval of irinotecan ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2005.04.022
更新日期:2005-12-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) appears to be one of the most active drugs in the treatment of advanced head and neck cancer. The maximum tolerated dose of paclitaxel in combination with carboplatin is currently being evaluated in phase I/II studies. We designed a phase II study to eval...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1997-02-01 00:00:00
abstract::The primary element involved in the practical delivery of hereditary cancer risk counseling is the development of a cancer genetics service. This service should involve a multidisciplinary core of specialists, aim to identify at-risk individuals and their families, and provide comprehensive genetic counseling with the...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2007.07.003
更新日期:2007-10-01 00:00:00
abstract::Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::The potential benefits of docetaxel (Taxotere; Aventis, Antony, France) to patients with previously-treated non-small cell lung cancer have been evaluated in two prospective randomized phase III trials. In one study, patients with stage IIIB/IV non-small cell lung cancer who had failed previous cisplatin-based chemoth...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:2001-02-01 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::Since its approval in 2011 for patients with recurrent glioblastoma (GBM), physicians have responded positively to the non-invasive nature of the NovoTTF-100A System device (NovoCure Ltd, Haifa, Israel), citing significantly less toxicity and a better quality of life profile compared to available conventional therapie...
journal_title:Seminars in oncology
pub_type:
doi:10.1053/j.seminoncol.2013.10.002
更新日期:2013-12-01 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::Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options and exceedingly high mortality rates. Currently, cure can only be achieved through resection, however the vast majority of patients present with advanced disease for which upfront surgery is not an option. In...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2018.12.002
更新日期:2019-02-01 00:00:00
abstract::Hypercalcemia of malignancy (HCM) is a potentially life-threatening complication of cancer resulting from increased bone resorption by osteoclasts. Clinical management of HCM primarily consists of intravenous rehydration therapy combined with pharmaceutical agents that decrease osteoclast activity. Several generations...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.37417
更新日期:2002-12-01 00:00:00
abstract::Intraoperative lymphatic mapping and selective lymphadenectomy for solid malignancies is a novel technique, having been introduced into surgical practice in the last 12 years. Dissemination of this technique among surgeons has followed a course similar to that found with the introduction of new laparoscopic techniques...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.03.005
更新日期:2004-06-01 00:00:00
abstract::For any tumor to become cancerous, various genetic mutations and biologic alterations must occur in the cell that in combination render it a malignant neoplasm. Small cell lung cancer (SCLC) is a neoplasm associated with several molecular and cellular abnormalities. SCLC is associated with early and frequent metastasi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2003.50019
更新日期:2003-02-01 00:00:00
abstract::Investigators representing all major melanoma research areas present an overview of the most important challenges for the field. Four major research areas are covered plus the training of new investigators. For each area we first describe the present status, its strengths and weaknesses, and then outline specific reco...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2007.09.004
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 studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II tr...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::We studied the pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin administered in combination to 21 patients with advanced non-small cell lung cancer. Paclitaxel was administered as a 24-hour intravenous infusion at doses of 135 to 200 mg/m2. Carboplatin, dosed to a tar...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::The availability of subcutaneously (SC) administered amifostine may present an advantage for radioprotectant therapy in head and neck cancer patients. In a randomized phase II trial comparing SC amifostine versus no amifostine in 140 patients undergoing radiation therapy for head and neck, thoracic, or pelvic cancers,...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1053/sonc.2002.37350b
更新日期:2002-12-01 00:00:00
abstract::High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units o...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1990-02-01 00:00:00
abstract::In spite of the chemosensitivity seen with the initial treatment of malignant lymphoid disorders, relapse is common and death most often occurs as a result of disease progression. This is related to a multitude of resistance mechanisms associated with the various lymphoproliferative disorders. As a result, therapies t...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::Richter syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate RS is ~0.5% per year of observation. Two biomarkers (NOTCH1 mutations and subset 8 configuration of the B-cell receptor) may help identifying...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2016.02.012
更新日期:2016-04-01 00:00:00