Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria.     

Antiangiogenic cancer therapy

Like most embryonic tissues, tumors have the ability to build up their own blood vessel networks. However, the architecture of tumor vessels is fundamentally different from that found in healthy tissues. Tumor vessels are usually irregular, heterogeneous, leaky, and poorly associated with mural cells. Endothelial cells in tumor vessels are also disorganized and express imbalanced surface molecules. These unusual features may provide some molecular and structural basis for selective inhibition or even destruction of tumor vessels by angiogenesis inhibitors. In animal tumor models, several angiogenesis inhibitors seem to inhibit tumor angiogenesis specifically without obvious effects on the normal vasculature. As a result, these inhibitors produced potent antitumor effects in mice. Excited by these preclinical studies, more than 60 angiogenesis inhibitors are being evaluated for their anticancer effects in human patients. Although the ultimate outcome of antiangiogenic clinical trials remains to be seen, several early observations have reported some disappointing results. These early clinical data have raised several important questions. Can we cure human cancers with angiogenesis inhibitors? Have we found the ideal angiogenesis inhibitors for therapy? What is the difference between angiogenesis in an implanted mouse tumor and in a spontaneous human tumor? What are the molecular mechanisms of these angiogenesis inhibitors? Should angiogenesis inhibitors be used alone or in combinations with other existing anticancer drugs? In this review, we will discuss these important issues in relation to ongoing antiangiogenic clinical trials.     

Antiangiogenic drugs in ovarian cancer

Ovarian cancer continues to be a major cause of morbidity and mortality in women. Antiangiogenic treatments have emerged as a promising strategy to treat ovarian cancer. This article reviews the rationale supporting the use of antiangiogenic treatments in ovarian cancer, the clinical development of this group of drugs and the toxicities specific to this modality of treatment.     

Antiangiogenic therapy for cancer: an update

The identification and characterization of several important regulators of angiogenesis, which led to Food and Drug Administration approval of the first antiangiogenic drugs, has opened a new era in cancer therapy. This article focuses on the clinical progress in targeting one of the major regulators of angiogenesis, vascular endothelial growth factor-A and also discusses some recent advances in the elucidation of potential cellular and molecular mechanisms underlying refractoriness or resistance to antiangiogenic therapies.     

外周T细胞淋巴瘤抗血管生成研究进展

 外周T细胞淋巴瘤（PTCL）对传统的化疗方案不敏感,与B细胞淋巴瘤相比预后差,目前缺乏有效的治疗方案。血管生成在恶性肿瘤的生长过程中具有重要的作用,研究显示血管内皮生长因子（VEGF）的表达与PTCL的临床特征及预后相关。同时,具有抗血管生成作用的药物在PTCL的初步临床研究中显示出了疗效。     

Gene therapy for ovarian cancer

Advances in molecular virology and biotechnology have led to the engineering of vectors that can efficiently transfer genes to target cells. Gene therapy strategies were developed along two lines: Cytotoxic approaches involve the transfer of genes that encode enzymes, which convert inactive prodrugs into cytotoxic drugs. Corrective gene therapy approaches aim to repair specific molecular alterations in signal transduction mechanisms that control the cell cycle or induce apoptosis. Clinical evidence suggests that gene therapies are best suited for patients with minimal residual disease. Multimodality approaches with conventional strategies and novel therapeutic tools in various combinations will most likely prove advantageous, compared to single-modality treatments. However, clinical trials will need to test these hypotheses.     

Salvage therapy for ovarian cancer

The majority of patients with ovarian cancer will relapse after initial chemotherapy and will be candidates for salvage treatment. Currently, five agents show clear activity in patients with platinum- and paclitaxel-resistant disease: topotecan, oral etoposide, liposomal doxorubicin, gemcitabine, and, possibly, docetaxel. In addition, other agents have activity in platinum-resistant patients: vinorelbine, tamoxifen, ifosfamide, altretamine, 5-fluorouracil with leucovorin, and, possibly, irinotecan. Furthermore, selected patients may benefit from other therapeutic approaches such as surgery or radiation therapy.     

Gene therapy for ovarian cancer

Ovarian cancer remains the leading cause of death due to gynecologic cancer in women in the United States. Gene and viral-based therapies represent novel therapeutic approaches for cancer. The manipulation of genetic content of tumor cells toward a therapeutic end has been divided into several general strategies, including molecular chemotherapy, mutation compensation, immunopotentiation, and virotherapy. Improvements in delivery vehicles and in evaluation of gene transfer and viral replication remain important areas of investigation. We highlight the most recent advances in these novel therapeutic approaches for ovarian cancer and include a summary of recent clinical trials.     

Antiangiogenic therapy in the management of breast cancer

An improved understanding of the important role of angiogenesis in tumor biology has led to development of different antiangiogenic therapies. Numerous clinical studies for several antiangiogenic agents have recently been conducted in breast cancer patients and have shown clinically significant improvement in outcomes. This review focuses on current progress in the field of antiangiogenic therapy in the management of breast cancer, also highlighting issues regarding future therapeutic development that result in the greatest clinical benefits and minimizing the adverse effects.     

Antiangiogenic agents as second-line therapy for advanced non-small cell lung cancer

With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target. Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents. This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy.     

乳腺癌抗血管生成治疗:现状与前景

Tumor angiogenesis plays an important role in the growth, invasion and metastasis of breast cancer, therefore re-cently a very active area of breast cancer research involves the addition of antiangiogenic therapy. Numerous clinical studies for several antiangiogenic agents have recently been conducted in breast cancer patients and have shown clinically significant improvement in outcomes. This review gives a brief background to breast cancer angiogenesis, also focusing on current prog-ress in the field of a...     

Salvage therapy for recurrent epithelial ovarian cancer

There are no comparative prospective trials to support dogmatic statements concerning the sequence and duration of therapy in the salvage setting. Although the literature offers many examples of chemotherapy studies conducted in the salvage setting, these studies typically involve relatively small numbers of younger patients whose disease shows good performance. The extrapolation of these observations to the practice setting, compounded by the clinical and molecular heterogeneity of epithelial ovarian cancer, further exacerbates the difficulties encountered in individual treatment recommendations.     

Postoperative abdominopelvic radiation therapy for ovarian cancer

From 1963 through 1984, 74 patients with Stage I, II, or III epithelial ovarian cancer who completed a total hysterectomy and debulking procedure and had less than 2 cm residual disease were treated with whole abdominal and pelvic boost radiation therapy (WAP) at Yale-New Haven Hospital. WAP consisted of a whole abdominal dose of 1750 to 2500 cGy (at 100-160 cGy per fraction) and a total pelvic dose of 4000-4600 cGy. Based on stage, amount of residual disease, pathologic type, and grade of tumor, the 74 patients were classified into a favorable group (FG) and an unfavorable group (UG) using the classification scheme developed at the Princess Margaret Hospital (PMH). The actuarial survival at 10 years for the FG patients was 77% (+/- 10%, 95% confidence limits) and for the UG patients was only 7% (+/- 13%). Local control of disease in the abdomen and pelvis was 87% in the FG and only 36% in the UG. Severe long-term complications occurred in 7% of the patients and consisted of small bowel obstruction. Our results strongly indicate that the PMH classification of FG and UG is useful in our patient population in determining which subgroup of patients should be offered WAP.