Combining Radiotherapy With Anti-angiogenic Therapy and Immunotherapy; A Therapeutic Triad for Cancer?

Goedegebuure, Ruben S.A.; Klerk, Leonie K. de; Bass, Adam J.; Derks, Sarah; Thijssen, Victor L.

doi:10.3389/fimmu.2018.03107

Cited by 82 publications

(79 citation statements)

References 181 publications

(194 reference statements)

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“…In previous studies, we reported the occurrence of EndMT in irradiated tumor and normal tissues after radiation therapy 18,61,82,83 . Radiation-induced EndMT causes fibrotic changes in both tumors and the normal tissue microenvironment, such as in the lungs and heart vessels, which contribute to tumor radioresistance and normal tissue damage, respectively.…”

Section: Endmt In Radiation Therapymentioning

confidence: 99%

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Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

et al. 2020

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Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy. Based on the known effects of EndMT on the cardiac toxicity of anticancer therapy and tissue damage of radiation therapy, we propose that EndMT can be targeted as a strategy for overcoming tumor resistance while reducing complications, such as tissue damage. In this review, we discuss EndMT and its roles in damaging cardiac and lung tissues, as well as EndMT-related effects on tumor vasculature and resistance in anticancer therapy. Modulating EndMT in radioresistant tumors and radiationinduced tissue fibrosis can especially increase the efficacy of radiation therapy. In addition, we review the role of hypoxia and reactive oxygen species as the main stimulating factors of tissue damage due to vascular damage and EndMT. We consider drugs that may be clinically useful for regulating EndMT in various diseases. Finally, we argue the importance of EndMT as a therapeutic target in anticancer therapy for reducing tissue damage.

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Section: Endmt In Radiation Therapymentioning

confidence: 99%

“…There is increasing interest in combining radiotherapy with antiangiogenic therapy or immunotherapy to further improve the effectiveness of radiotherapy (Fig. 1) 83 .…”

Section: Radiation-induced Tumor Endmtmentioning

confidence: 99%

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

et al. 2020

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“…It has demonstrated that ORR is changing from 39 to 62% for RT in HCC patients with PVTT (12,(22)(23)(24). Although RT alone could achieve a high locoregional tumor control rate, combining systemic treatments with RT seems necessary because of the failure outside the radiation field (12,25). Proper tumor oxygenation is good for enhancing the RT efficacy, so improvement of tumor hypoxia has been explored using antiangiogenic agents.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of SBRT Combined With Camrelizumab and Apatinib in HCC Patients With PVTT: Study Protocol of a Randomized Controlled Trial

Qin

et al. 2020

Front. Oncol.

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Background: Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) has poor prognosis. Sorafenib/lenvatinib is recommended as the first-line therapy in these patients currently, with unsatisfactory response and survival benefit reported. Radiotherapy (RT) is increasingly utilized in advanced HCC and is considered an alternative option for HCC patients with PVTT. Combined treatment of RT and locoregional treatments such as transarterial chemoembolization shows promising results. However, the efficacy and safety for combined treatment of RT and systemic therapy have not been reported and thus warrant further studies. This prospective clinic trial aims at evaluating the efficacy and safety of stereotactic body RT (SBRT) combined with camrelizumab and apatinib in HCC patients with PVTT. Methods: This multicenter, open-label, randomized controlled trial will enroll 264 HCC patients with PVTT who have not received systemic therapy previously. Stratification of patients will be based on the presence or absence of extrahepatic metastasis and level of AFP (AFP ≥ 400 or <400 ng/mL) and randomly assigned 1:1 to study and control groups. Patients in study group will receive SBRT (95% PTV 36-40 Gy/6-8 Gy), camrelizumab (200 mg every 3 weeks), and apatinib (250 mg every day), and patients in control group will receive camrelizumab (200 mg every 2 weeks) and apatinib (250 mg every day). Patients will be followed up for 1.5 to 3.5 years since the start of therapy. We will use overall survival as the primary endpoint and progression-free survival, objective response rate, disease control rate, adverse events, and quality of life as the secondary endpoints. Discussion: This study will be the first randomized controlled trial to assess the efficacy and safety of SBRT combined with camrelizumab and apatinib for HCC patients with PVTT. The results may help establish a new standard first-line therapy for these patients.

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“…Single, large ablative doses of radiation may particularly hamper effective antitumour immune responses; thus, focus has been on fractionated radiation regimens and SBRT protocols . SBRT is theoretically less systemically immunosuppressive than conventional radiation, in which patients have circulating lymphocytes that may be irradiated over 5 to 6 weeks .…”

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

“…126,156 Single, large ablative doses of radiation may particularly hamper effective antitumour immune responses; thus, focus has been on fractionated radiation regimens and SBRT protocols. 60,157,158 SBRT is theoretically less systemically immunosuppressive than conventional radiation, in which patients have circulating lymphocytes that may be irradiated over 5 to 6 weeks. 60,126 Early studies have demonstrated that immunotherapy and radiation can safely be administered together and may induce responses, [159][160][161][162] but questions remain regarding the optimal timing of systemic treatment with radiation, radiation dose, and tumour volume irradiated.…”

Section: Rt and Immunotherapy For Sarcomasmentioning

confidence: 99%

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Borgatti

Dickerson

Lawrence

2019

Vet Comparative Oncology

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Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low‐grade sarcomas and remains the standard therapeutic approach. For advanced, high‐grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of “Coley's toxins” in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype‐specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming.

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Combining Radiotherapy With Anti-angiogenic Therapy and Immunotherapy; A Therapeutic Triad for Cancer?

Cited by 82 publications

References 181 publications

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

Efficacy and Safety of SBRT Combined With Camrelizumab and Apatinib in HCC Patients With PVTT: Study Protocol of a Randomized Controlled Trial

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

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