Abstract:
:Antisense oligonucleotides (ASONs) are one of the new classes of molecularly targeted agents that have transitioned from the laboratory into clinical trials. Rational drug design has resulted in agents directed against a number of important cellular targets, including the mRNA of bcl-2, protein kinase (PK) C-alpha, PKA-I, H-ras, c-raf, R1 and R2 subunit of ribonucleotide reductase, and transforming growth factor beta2. These drugs are well tolerated with favorable toxicity profiles, and preliminary studies have demonstrated that they can be feasibly combined with chemotherapy. Plasma half-life is short, generally necessitating continuous prolonged intravenous infusion. Shorter administration schedules are being investigated. Efficacy has been demonstrated in early-phase studies in non-small-cell lung cancer (NSCLC), non-Hodgkin's lymphoma, ovarian cancer, melanoma, and prostate cancer. Molecular correlative studies with peripheral blood mononuclear cells and tumor tissue have demonstrated suppression of target proteins, suggesting that these drugs are indeed reaching the target. Here we discuss the current status of development of ASONs, focusing on LY900003 (formerly ISIS 3521), an agent directed against PKC-alpha currently under study in NSCLC. Phase III studies will determine the ultimate role these agents will play in the treatment of cancer. Future areas of study include combination with radiation and other molecularly targeted agents, alternative dosing schedules, liposomal administration, and the development of new antisense agents directed against additional molecular targets.
journal_name
Clin Lung Cancerjournal_title
Clinical lung cancerauthors
Davies AM,Gandara DR,Lara PN Jr,Mack PC,Lau DH,Gumerlock PHdoi
10.3816/clc.2003.s.007keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
S68-73eissn
1525-7304issn
1938-0690pii
S1525-7304(11)70313-8journal_volume
4 Suppl 2pub_type
杂志文章abstract:INTRODUCTION:The effect of local therapy (LT) for oligoprogressive epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) has not been well established. Forty-six patients with stage IIIB/IV EGFR-mutated NSCLC were treated by LT and continuing tyrosine kinase inhibitors (TKIs) for oligoprogr...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2017.04.002
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Cancer-associated macrophage-like cells (CAMLs) are a potential peripheral blood biomarker for disease progression. This study used data from a phase 2 clinical trial to evaluate prognostic utility of CAMLs for locally advanced non-small-cell lung cancer treated with definitive chemoradiotherapy (CRT) and at...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.06.016
更新日期:2020-06-20 00:00:00
abstract:BACKGROUND:The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven non-small-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2015.02.002
更新日期:2015-09-01 00:00:00
abstract::Historically, malignant pleural mesothelioma patients with potentially resectable disease have been treated with surgery and radiation alone. With improvements in systemic and intrapleural treatment options, a movement toward multi-modality therapy has become more common. Systemic treatment options largely consist of ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2009.n.005
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:First-line treatment of non-small-cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune checkpoint inhibitor (ICI). Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of ICIs through blockade of vascular endothelial growth ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.03.010
更新日期:2020-09-01 00:00:00
abstract:INTRODUCTION:We set out to investigate whether volumetric tumor measurements allow for a prediction of treatment response, as measured by patient survival, in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS:Patients with nonresectable NSCLC (stage III or IV, n = 100) who were repeatedl...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.11.001
更新日期:2014-03-01 00:00:00
abstract::Expert consensus guidelines have defined minimum requirements for routine testing and identification of classical epidermal growth factor (EGFR) mutations (ie, exon 19 deletions and exon 21 L858R substitution) and anaplastic lymphoma kinase (ALK) rearrangements in advanced non-small-cell lung cancers of adenocarcinoma...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.1016/j.cllc.2016.05.016
更新日期:2016-11-01 00:00:00
abstract:INTRODUCTION:The field of biomarker development is evolving to assist in determining benign from malignant pulmonary nodules. Although a prospective clinical utility would best to show how a biomarker affects patient treatment and outcomes, we sought to begin to understand how the results might alter management by dete...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2019.05.004
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:Subdivisions of N2 non-small-cell lung cancer (NSCLC) cases based on metastatic status of mediastinal and non-mediastinal lymph nodes have been proposed. This study aimed to evaluate N2 disease classification by mediastinal lymph nodes alone. PATIENTS AND METHODS:We reviewed 187 patients with NSCLC pN1-N2 w...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.04.012
更新日期:2013-11-01 00:00:00
abstract::After decades of platinum-based chemotherapy for advanced small-cell lung cancer, there has finally been a therapeutic advance. The combination of a platinum chemotherapy, etoposide, and an immune checkpoint inhibitor has yielded overall survival benefits in two successive phase 3 trials. Unfortunately, these trials o...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2020.04.006
更新日期:2020-11-01 00:00:00
abstract:INTRODUCTION:Economic analyses of upcoming treatments for lung cancer benefit from real-world health utility scores (HUSs) in an era of targeted therapy. METHODS:A longitudinal cohort study at Princess Margaret Cancer Centre evaluated 1571 EQ5D-3L-derived HUSs in 475 outpatients with metastatic lung cancer across vari...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.12.015
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized. ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.03.011
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:The optimal treatment of locally advanced non-small-cell lung cancer (NSCLC) remains controversial. We hypothesized that using a trimodality approach in selected patients with stage IIIA/IIIB disease would be both feasible and efficacious with reasonable toxicity. PATIENTS/METHODS:We enrolled 13 patients wi...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2011.06.003
更新日期:2011-09-01 00:00:00
abstract::Viruses capable of inducing lysis of malignant cells through their replication process are known as "oncolytic" viruses. Clinical trials in oncology have been performed with oncolytic viruses for nearly fifty years. Both systemic and intratumoral routes of administration have been explored. Toxicity has generally been...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.1999.n.003
更新日期:1999-08-01 00:00:00
abstract::Novel therapies have been added to the treatment arsenal of physicians treating lung cancer in recent years. Most promising are agents that target the major pathways involved in cancer evolution, mostly proliferation and angiogenesis. Some of these treatments have been shown to synergize with traditional chemotherapy ...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/CLC.2008.s.014
更新日期:2008-01-01 00:00:00
abstract::Current treatments of non-small-cell lung cancer (NSCLC) are inadequate and new therapies are being developed that target specific cellular signaling proteins associated with tumor growth. One potential target is protein kinase C (PKC)-alpha, a signaling molecule with an important role in cell regulation and prolifera...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2004.n.032
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model. PATIENTS AND ME...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.01.006
更新日期:2018-07-01 00:00:00
abstract::The Lung Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative first met in January of 1994. Included in the membership were three pathologists who, with the other members of the DSG, felt that a useful contribution to the work of the group would be a recommendation on standardized ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/clc.2000.n.008
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:Afatinib is approved in the US, Europe, and several other regions for first-line treatment for epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:Treatment-naive patients with advanced EGFRm+ NSCLC were randomized to afatinib (40 mg/d) versus...
journal_title:Clinical lung cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.cllc.2018.03.009
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Many patients diagnosed with stage IIIB (AJCC sixth edition; T4, N3, or both; no pleural effusion) non-small-cell lung cancer (NSCLC) are treated with curative intent, despite a low cure rate. Guidelines are required to help select patients for radical therapy so that the patients with little chance of cure ...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2013.12.007
更新日期:2014-05-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is regulated by the hypoxia-inducible factor 1 (HIF1) pathway and is implicated in tumor progression and patient survival in many types of cancer. Insulin-like growth factor-binding protein 3 (IGFBP3) is also regulated by HIF1 but works in a completely different manner by modu...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2004.n.011
更新日期:2004-03-01 00:00:00
abstract::This article describes the treatment rationale and study-related procedures for the A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small-Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL) st...
journal_title:Clinical lung cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.cllc.2012.06.007
更新日期:2012-11-01 00:00:00
abstract::Two cases of complications secondary to the use of microwave ablation (MWA) in non-small-cell lung cancer (NSCLC) are discussed herein. The first case involves a 62-year-old man with stage IB NSCLC who declined surgery and pursued MWA. Within 7 months, he had residual disease at the MWA treatment site, and surgery was...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.3816/CLC.2008.n.019
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. PATIENTS AND METHODS:Two hundred and seventy seven patients diagnosed in our i...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2011.03.019
更新日期:2011-05-01 00:00:00
abstract:INTRODUCTION:Frailty of surgical patients has been associated with worse outcomes. There is limited literature discussing frailty in patients with lung cancer treated with stereotactic body radiotherapy (SBRT). This study assesses the relationship between frailty and overall survival (OS), tumor control, and toxicity i...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2018.05.008
更新日期:2018-09-01 00:00:00
abstract:INTRODUCTION:We examined the effect of access to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on survival for Asian female (AF) EGFR mutation-enriched patients with advanced lung adenocarcinoma. MATERIALS AND METHODS:We used the Surveillance Epidemiology and End Results database to s...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.08.008
更新日期:2017-01-01 00:00:00
abstract::Although radical surgery remains the mainstay therapeutic modality for early-stage non-small-cell lung cancer (NSCLC), long-term survival of patients with completely resected NSCLC tumors remains suboptimal. Globally, the 5-year survival rate of patients who undergo complete surgical resection is in the range of 40%-5...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.3816/clc.2004.s.016
更新日期:2004-12-01 00:00:00
abstract::During the past decade, the recognition of an ever-expanding list of driver oncogenic mutations in non-small-cell lung cancer has resulted in rapid therapeutic advances. Since the first description of the echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement in 4% of case...
journal_title:Clinical lung cancer
pub_type: 杂志文章,评审
doi:10.1016/j.cllc.2016.05.006
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Molecular studies have demonstrated actionable driver oncogene alterations are more frequent in never-smokers with non-small-cell lung cancer (NSCLC). The etiology of these driver oncogenes in patients with NSCLC remains unknown, and environmental tobacco smoke (ETS) is a potential cause in these cases. MAT...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2017.01.005
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:The lung is a heterogeneous organ with relative overperfusion of the lung bases. We determined whether a lower lobe primary tumor location was associated with poor outcomes in the setting of stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). PATIENTS AND ME...
journal_title:Clinical lung cancer
pub_type: 杂志文章
doi:10.1016/j.cllc.2016.09.001
更新日期:2017-03-01 00:00:00