Update on novel agents in renal cell carcinoma

Tamaskar, Ila; Пили, Роберто

doi:10.1586/era.09.157

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…Of many explored in clinical trials, three have been approved for clinical use; two small molecule TKIs in monotherapy (sorafenib, sunitinib) for metastatic renal and hepatocellular carcinoma and an anti-VEGF monoclonal antibody (bevacizumab) in combination with chemotherapy for metastatic colorectal cancer, NSCLC and breast cancer 97–101. Today none of these agents is approved in combination with radiation therapy.…”

Section: Clinical Trials On Radiation and Vascular-targeted Therapiesmentioning

confidence: 99%

Radiotherapy in combination with vascular-targeted therapies

Ciric¹,

Serša²

2010

Radiology and Oncology

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BackgroundGiven the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable.ConclusionsStrong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised.

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Section: Clinical Trials On Radiation and Vascular-targeted Therapiesmentioning

confidence: 99%

Radiotherapy in combination with vascular-targeted therapies

Ciric¹,

Serša²

2010

Radiology and Oncology

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“…Indeed, a mAb against vascular endothelial growth factor (VEGF), bevacizumab, showed clinical activity against ovarian cancer in a phase 3 clinical trial . Although the effectiveness of anti‐angiogenic drugs is encouraging, resistance to anti‐angiogenic therapy has been reported in several review articles . To overcome these problems, novel strategies for anti‐angiogenic therapy must be developed.…”

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confidence: 99%

In vivo delivery of siRNA targeting vasohibin‐2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer

et al. 2013

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Vasohibin‐2 (VASH2) is a homolog of vasohibin‐1 and exhibits pro‐angiogenic activity. We recently reported that VASH2 is expressed in certain ovarian cancers and promotes tumor growth through angiogenesis. To further demonstrate the effectiveness of molecular targeting of VASH2 for anticancer treatment, we applied in vivo delivery of siRNA targeting VASH2 (siVASH2) using atelocollagen to a xenograft model of ovarian cancer. We inoculated mice s.c. with DISS and SKOV‐3, two representative human ovarian serous adenocarcinoma cell lines. When tumors were measurable, we initiated treatment with control or siVASH2 mixed with atelocollagen, which enveloped the whole tumor. Treatment with siVASH2 significantly inhibited s.c. tumor growth by abrogating tumor angiogenesis. We confirmed that expression of VASH2 mRNA in the tumor was downregulated by siVASH2 treatment. In addition, the siVASH2‐treated tumor contained more blood vessels covered with pericytes, indicating that knockdown of VASH2 contributes to the normalization of tumor blood vessels. Based on these results, VASH2 may be a promising molecular target for ovarian cancer treatment.

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“…RCC one of the malignancies most resistant to conventional cytotoxic chemotherapy 6. Moreover, up to 40%–50% of patients who undergo curative renal resection go on to develop metastatic or advanced RCC 7,8. The 5-year survival rates for patients with kidney cancer, according to the American Joint Committee on Cancer staging classification, are 81% for stage I, 74% for stage II, 53% for stage III, and 8% for stage IV 4.…”

Section: Introductionmentioning

confidence: 99%

Targeted treatments in advanced renal cell carcinoma: focus on axitinib

Verzoni¹,

Grassi²,

Testa³

et al. 2014

PGPM

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Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.

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Update on novel agents in renal cell carcinoma

Cited by 15 publications

References 56 publications

Radiotherapy in combination with vascular-targeted therapies

Radiotherapy in combination with vascular-targeted therapies

In vivo delivery of siRNA targeting vasohibin‐2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer

Targeted treatments in advanced renal cell carcinoma: focus on axitinib

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