oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Targeted Therapy in Nonmelanoma Skin Cancers  [PDF]
Giulia Spallone,Elisabetta Botti,Antonio Costanzo
Cancers , 2011, DOI: 10.3390/cancers3022255
Abstract: Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.
Targeted Therapy in Hepatocellular Carcinoma  [PDF]
Clarinda W. L. Chua,Su Pin Choo
International Journal of Hepatology , 2011, DOI: 10.4061/2011/348297
Abstract: Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, as well as a common cause of cancer-related death. HCC frequently occurs in the setting of a diseased cirrhotic liver and many patients present at an advanced stage of disease. Together with a poor functional status, this often precludes the use of systemic therapy, especially conventional cytotoxic drugs. Moreover, HCC is known to be a relatively chemo-refractory tumor. There have been many targeted drugs that have shown potential in the treatment of HCC. Many clinical trials have been carried out with many more in progress. They include trials evaluating a single targeted therapy alone, two or more targeted therapy in tandem or a combination of targeted therapy and conventional chemotherapy. In this article, we seek to review some of the more important trials examining the use of targeted therapy in HCC and to look into what the future holds in terms of targeted treatment of HCC.
Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma: A Review of the Historical Literature and Its Role in the Era of Targeted Molecular Therapy  [PDF]
Muhammad Z. Aslam,P. N. Matthews
ISRN Urology , 2014, DOI: 10.1155/2014/717295
Abstract: Renal cell carcinoma presents with metastatic disease in approximately 30% cases. While surgical intervention remains the standard of care for organ confined disease, its role is limited in the management of metastatic disease. Over the last decade, cytoreductive nephrectomy prior to immunotherapy has demonstrated significant improvement in overall survival for appropriately selected patients. This review summarizes the evidence for the role of cytoreductive nephrectomy in combination with immunotherapy and discusses its potential role in the current era of targeted molecular therapy. 1. Introduction Renal cell carcinoma (RCC) accounts for approximately 5% of epithelial cancers worldwide [1] with clear cell RCC representing 85% of these cancers [2]. 30% of patients with RCC are found to have metastatic disease on staging investigations and roughly one-third of patients with organ confined disease undergoing nephrectomy eventually develop metastases [3]. Metastatic RCC (mRCC) is known to have a poor outcome with 2-year median survival rate of only 10–20% [4]. Historically, cytokine based immunotherapies have remained the mainstay of treatment for mRCC [5, 6], until more recently that has been replaced by targeted molecular therapies [7]. Radical nephrectomy as a treatment option in mRCC, (sometimes called debulking or cytoreductive nephrectomy (CRN)) is often indicated as part of an integrated management strategy. It has been previously described in historical series [8], but it was widely accepted as an effective form of treatment in combination with postoperative immunotherapy after the results of 2 prospective randomized trials were published [9, 10]. Previously, nephrectomy had been performed in mRCC patients largely as a palliative measure for control of pain, haemorrhage, paraneoplastic syndromes, and symptoms related to compression of adjacent viscera. It has been reported that nephrectomy performed for these palliative measures can result in spontaneous regression of metastases in up to 4% of cases [11]. Though the exact mechanism of these regression remains unknown, possible explanation could be that nephrectomy might remove a source of tumour-promoting growth factors or immunosuppressive cytokines [12]. 2. The Historical Series There was some evidence in historical series that patients treated with immunotherapy respond better if they have previously undergone nephrectomy. Walther et al. [8] studied 93 patients with the clinical diagnosis of mRCC and manifestations of paraneoplastic syndromes who underwent removal of the primary tumor, as well
Targeted medical therapy of biliary tract cancer: Recent advances and future perspectives  [cached]
Michael H?pfner, Detlef Schuppan, Hans Scherübl
World Journal of Gastroenterology , 2008,
Abstract: The limited efficacy of cytotoxic therapy for advanced biliary tract and gallbladder cancers emphasizes the need for novel and more effective medical treatment options. A better understanding of the specific biological features of these neoplasms led to the development of new targeted therapies, which take the abundant expression of several growth factors and cognate tyrosine kinase receptors into account. This review will briefly summarize the status and future perspectives of antiangiogenic and growth factor receptor-based pharmacological approaches for the treatment of biliary tract and gallbladder cancers. In view of multiple novel targeted approaches, the rationale for innovative therapies, such as combinations of growth factor (receptor)-targeting agents with cytotoxic drugs or with other novel anticancer drugs will be highlighted.
Targeted Therapy in Hepatocellular Carcinoma  [PDF]
Clarinda W. L. Chua,Su Pin Choo
International Journal of Hepatology , 2011, DOI: 10.4061/2011/348297
Abstract: Hepatocellular carcinoma (HCC) is one of the commonest cancers worldwide, as well as a common cause of cancer-related death. HCC frequently occurs in the setting of a diseased cirrhotic liver and many patients present at an advanced stage of disease. Together with a poor functional status, this often precludes the use of systemic therapy, especially conventional cytotoxic drugs. Moreover, HCC is known to be a relatively chemo-refractory tumor. There have been many targeted drugs that have shown potential in the treatment of HCC. Many clinical trials have been carried out with many more in progress. They include trials evaluating a single targeted therapy alone, two or more targeted therapy in tandem or a combination of targeted therapy and conventional chemotherapy. In this article, we seek to review some of the more important trials examining the use of targeted therapy in HCC and to look into what the future holds in terms of targeted treatment of HCC. 1. Introduction Liver cancer is the sixth most common cancer worldwide, accounting for 5.7% of new cancer cases, and the third most common cause of cancer-related death [1]. The majority of cases and deaths occur in developing countries. Of the primary liver tumors in adults, hepatocellular carcinoma (HCC) is the commonest [2]. HCC frequently occurs in the setting of a diseased cirrhotic liver. It has well-defined risk factors, the most common being infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Chronic excessive alcohol consumption, environmental toxins, for example, aflatoxin B and nonalcoholic steatohepatitis (NASH), make up the rest of the main causes. The etiological factors vary by geographical locations [3]. In Africa and East Asian countries including Taiwan, China, and Korea, HBV is the main cause whereas in the West and in Japan, HCV is the main risk factor, together with other causes of cirrhosis including alcohol [3, 4]. The asymptomatic nature of a HBV and HCV carrier state, the insidious presentation of early HCC, and screening programs that are not properly defined or adhered to results in the majority of patients with HCC presenting at an intermediate or advanced state. Potentially curative strategies such as resection and transplantation as well as loco-regional therapies such as radiofrequency ablation and transarterial chemoembolization are often not possible at these stages. Systemic treatment with chemotherapy is not routinely employed in the treatment of advanced HCC for a variety of reasons. As HCC usually occurs in the context of a diseased cirrhotic liver,
Advances of Molecular Subtype and Targeted Therapy of Lung Cancer  [cached]
Lan SHAO,Zhengbo SONG,Yiping ZHANG,Dan SU
Chinese Journal of Lung Cancer , 2012, DOI: 10.3779/j.issn.1009-3419.2012.09.07
Abstract: The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, has created new opportunities for targeted therapy. Each subtype is associated with molecular tests that define the subtype and drugs that may have potential therapeutic effect on lung cancer. In 2004, mutations in the epidermal growth factor receptor (epidermal growth factor receptor, EGFR) gene were discovered in non-small cell lung cancers (NSCLC), especially in adenocarcinomas. And they are strongly associated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Moreover, in 2007 the existence of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene was discovered in NSCLC, and the same as EGFR-TKIs, ALK inhibitors are being found to be highly effective in lung cancers. At present, multiple molecular subtype of lung cancer and relevant targeted drugs are undering study. Here, we review the remarkable progress in molecular subtype of lung cancer and the related targeted therapy.
Anti-EGFR-Targeted Therapy for Esophageal and Gastric Cancers: An Evolving Concept  [PDF]
Tomislav Dragovich,Christopher Campen
Journal of Oncology , 2009, DOI: 10.1155/2009/804108
Abstract: Cancers of the esophagus and stomach present a major health burden worldwide. In the past 30 years we have witnessed some interesting shifts in terms of epidemiology of esophago gastric cancers. Regardless of a world region, the majority of patients diagnosed with esophageal or gastric cancers die from progression or recurrence of their disease. While there are many active cytotoxic agents for esophageal and stomach cancers, their impact on the disease course has been modest at best. Median survival for patients with advanced gastroesophageal cancer is still less than a year. Therefore, novel strategies, based on our understanding of biology and genetics, are desperately needed. Epidermal growth factor receptor (EGFR) pathway has been implicated in pathophysiology of many epithelial malignancies, including esophageal and stomach cancers. EGFR inhibitors, small molecule tyrosine kinase inhibitors and monoclonal antibodies, have been explored in patients with esophageal and gastric cancers. It appears that tumors of the distal esophagus and gastroesophageal junction (GEJ) may be more sensitive to EGFR blockade than distal gastric adenocarcinomas. Investigations looking into potential molecular predictors of sensitivity to EGFR inhibitors for patients with esophageal and GEJ cancers are ongoing. While we are still searching for those predictors, it is clear that they will be different from ones identified in lung and colorectal cancers. Further development of EGFR inhibitors for esophageal and GEJ cancers should be driven by better understanding of EGFR pathway disregulation that drives cancer progression in a sensitive patient population.
Recent advances of novel targeted therapy for squamous cell carcinoma of the head and neck  [cached]
Jed A. Katzel,Michael P. Fanucchi,William A. Cook,Zujun Li
Oncology Reviews , 2011, DOI: 10.4081/89
Abstract: Targeted therapies have proven beneficial for patients suffering from a number of different malignancies, including cancers of the head and neck. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor has shown benefit in combination with radiation for untreated patients or as a single agent for patients with platinum resistant disease. Cetuximab is the only targeted agent currently approved by the Federal Drug Administration for the treatment of head and neck cancer. A number of other agents have shown promising initial results including intracellular tyrosine kinase inhibitors, agents targeting vascular endothelial growth factor receptor, as well as other classes of novel therapies. Some of the data supporting the use of targeted therapy, including agents not yet approved in head and neck cancer, will be presented in this review. As our understanding of the cancer cell signaling pathways and novel targeted agents increases, the potential for treatment with reduced toxicity and improved clinical outcomes will become a reality.
Imatinib: A Breakthrough of Targeted Therapy in Cancer  [PDF]
Nida Iqbal,Naveed Iqbal
Chemotherapy Research and Practice , 2014, DOI: 10.1155/2014/357027
Abstract: Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology. 1. Introduction Imatinib (also known as “Gleevec” or “Glivec”), a tyrosine kinase inhibitor, was called as “magical bullet,” when it revolutionized the treatment of chronic myeloid leukemia (CML) in 2001. Imatinib was invented in the late 1990s by biochemist Nicholas Lyndon then working for Ciba-Geigy (now Novartis), and its use to treat CML was driven by Brian Druker, an oncologist at the Dana-Farber Institute. The first clinical trial of Imatinib took place in 1998 and the drug received FDA approval in May 2001. Lyndon, Druker, and the other colleagues were awarded the Lasker-DeBakey Clinical Medical Research Award in 2009 for “converting a fatal cancer into a manageable condition” and the Japan Prize in 2012 for their part in “the development of a new therapeutic drug targeting cancer-specific molecules.” Encouraged by the success of Imatinib in treating CML patients, scientists explored its effect in other cancers and it was found to produce a similar miracle effect in other cancers where tyrosine kinases were overexpressed. This review discusses the clinical implications of Imatinib in various cancers. 2. Clinical Pharmacology Tyrosine kinases are important mediators of the signaling cascade, determining key roles in diverse biological processes like growth, differentiation, metabolism, and apoptosis in response to external and internal stimuli. Deregulation of protein kinase activity has been shown to play a central role in the pathogenesis of human cancers. Imatinib, a 2-phenyl amino pyrimidine derivative, is a tyrosine kinase inhibitor with activity against ABL, BCR-ABL, PDGFRA, and c-KIT. The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is the
New Molecular Targeted Therapy and Redifferentiation Therapy for Radioiodine-Refractory Advanced Papillary Thyroid Carcinoma: Literature Review  [PDF]
Kai-Pun Wong,Brian Hung-Hin Lang
Journal of Thyroid Research , 2012, DOI: 10.1155/2012/818204
Abstract: Although the majority of papillary thyroid carcinoma could be successfully managed by complete surgical resection alone or resection followed by radioiodine ablation, a small proportion of patients may develop radioiodine-refractory progressive disease which is not amenable to surgery, local ablative treatment or other treatment modalities. The use of FDG-PET/CT scan for persistent/recurrent disease has improved the accuracy of restaging as well as cancer prognostication. Given that patients with RAI-refractory disease tend to do significantly worse than those with radioiodine-avid or non-progressive disease, an increasing number of phase I and II studies have been conducted to evaluate the efficacy of new molecular targeted drugs such as the tyrosine kinase inhibitors and redifferentiation drugs. The overall response rate of these drugs ranged between 0–53%, depending on whether the patients had been previously treated with these drugs, performance status and extent of disease. However, drug toxicity remains a major concern in administration of target therapies. Nevertheless, there are also ongoing phase III studies evaluating the efficacy of these new drugs. The aim of the review was to summarize and discuss the results of these targeted drugs and redifferentiation agents for patients with progressive, radioiodine-refractory papillary thyroid carcinoma. 1. Introduction Papillary thyroid carcinoma (PTC) is the most common type of differentiated thyroid carcinoma (DTC) and its age-adjusted incidence has doubled in the last 25 years [1]. Despite its relatively good prognosis with a 10-year cancer-specific survival above 90%, locoregional recurrences and distant metastasis do occur not infrequently [2]. Of the 5–20% patients who may develop locoregional recurrences, approximately two-thirds of these recurrences involved the cervical lymph nodes. On the other hand, up to 10–15% patients would either present with distant metastasis at diagnosis or develop distant metastasis some time after initial treatment [3]. It is not uncommon to encounter patients with initial persistent locoregional recurrence who also later develop distant metastasis. Perhaps, this is a sign of disease progression. Since most patients would have had a total thyroidectomy and radioiodine (RAI) ablation as their initial therapy, disease monitoring or surveillance often relies on regular measurement of thyroglobulin (Tg) and high resolution neck ultrasound (USG) [4]. FDG-PET/CT scan is now often used as a staging tool in patients with suspected disease recurrence. In terms of treating
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.