Radiotherapy in combination with vascular-targeted therapies

Abstract

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.

Clinical Response to Apatinib Combined With Brain Radiotherapy in EGFR Wild-Type and ALK-Negative Lung Adenocarcinoma With Multiple Brain Metastases

“…Several preclinical and clinical trials have proved the safety and efficacy of apatinib as a part of anti-angiogenic treatment (16,17); it was shown that apatinib can "normalize" tumor blood vessels and reduce vascular permeability. Furthermore, apatinib may increase oxygenation by normalization of tumor vasculature and regulation of the tumor microenvironment, thus increasing overall radiosensitivity (18). Taken together, these were some factors leading to the use of apatinib in this patient, along with ease of administration and lower costs as compared with intravenous bevacizumab.…”

Metronomic Chemotherapy and Radiotherapy as Salvage Treatment in Refractory or Relapsed Pediatric Solid Tumours

“…Antiangiogenic treatment normalizes tumour vasculature and oxygenation 24 . A combination of rt and mctx can lead to better clinical efficacy in various cancers, because antiangiogenic therapy increases oxygenation and radiosensitivity 23,25 , augmenting radiation efficacy 26 . Our findings might confirm a study reported by Sterba et al 15 , who showed encouraging results for rt combined with metronomic temozolomide in children with medulloblastoma.…”

Modern Ideas About the Combination of Radiation Therapy With Antiangiogenic Drugs in the Treatment of Patients With Brain Metastases

“…Учитывая ключевую роль гипоксии в радиоустойчивости, ингибиторы ангиогенеза, такие как ингибиторы VEGF, могут представлять интерес для разрушения этого порочного круга между ангиогенезом и радиорезистентностью путем нормализации сосудистой сети опухоли. Эта нормализация снижает гипоксию и улучшает радиочувствительность раковых клеток и эндотелиальных клеток [35][36][37]. Также не отмечено увеличения токсичности или кровоизлияния в мозг при совместном применении бевацизумаба с облучением всего головного мозга с использованием стандартного фракционирования лучевой терапии.…”