Trends and Challenges in Tumor Anti-Angiogenic Therapies

Jászai, József; Schmidt, Mirko H. H.

doi:10.3390/cells8091102

Cited by 171 publications

(132 citation statements)

References 293 publications

(497 reference statements)

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“…As angiogenesis plays a critical role in tumor growth and progression, a number of anti-angiogenic agents have been developed, but the response rates have been low. Among the disadvantages of anti-angiogenesis therapy are the lack of predictive biomarkers to distinguish responders from non-responders, drug resistance, and the involvement of many factors in the regulation of angiogenesis [131,132]. However, the high stability and accessibility of miRNAs in biofluids, their altered expression in tumor angiogenesis, and their capacity to target multiple transcripts [42] suggest that miRNAs can serve as predictive biomarkers while their inhibition of angiogenesis may provide a therapeutic option in many different cancers.…”

Section: Discussionmentioning

confidence: 99%

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Leone

Buonavoglia

Fasano

et al. 2019

JCM

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One of the hallmarks of cancer is angiogenesis, a series of events leading to the formation of the abnormal vascular network required for tumor growth, development, progression, and metastasis. MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs whose functions include modulation of the expression of pro- and anti-angiogenic factors and regulation of the function of vascular endothelial cells. Vascular-associated microRNAs can be either pro- or anti-angiogenic. In cancer, miRNA expression levels are deregulated and typically vary during tumor progression. Experimental data indicate that the tumor phenotype can be modified by targeting miRNA expression. Based on these observations, miRNAs may be promising targets for the development of novel anti-angiogenic therapies. This review discusses the role of various miRNAs and their targets in tumor angiogenesis, describes the strategies and challenges of miRNA-based anti-angiogenic therapies and explores the potential use of miRNAs as biomarkers for anti-angiogenic therapy response.

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Section: Discussionmentioning

confidence: 99%

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Leone

Buonavoglia

Fasano

et al. 2019

JCM

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“…Moreover, LCL‐SIM + LCL‐5‐FU did not affect the production of other antiangiogenic/antiinflammatory proteins, PF‐4 and IL‐12p70, in THE C26 colon carcinoma microenvironment (Table B), which could also contribute the beneficial outcome of this treatment. To support these data, the new concept of targeting angiogenesis, so‐called vascular normalization, is based on the suppression of proangiogenic factors and the preservation of antiangiogenic molecules in the tumor microenvironment . Thus, the restoration of intratumor vessel structure and function could increase blood perfusion and finally benefit other cancer therapies (including chemotherapy).…”

Section: Discussionmentioning

confidence: 99%

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5‐fluorouracil in vivo

et al. 2020

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5-Fluorouracil-based therapy remains the main approach in colorectal cancer, even though there are still some drawbacks, such as chemoresistance. In this study we combined 5-fluorouracil encapsulated in long-circulating liposomes with simvastatin, also encapsulated in long-circulating liposomes, that was previously proved to exert antitumor actions on the same tumor model. The production of angiogenic/inflammatory proteins was assessed by protein array and the production of markers for tumor aggressiveness (Bcl-2, Bax, and nuclear factor [NF]-κB) were determined by western blot analysis. Intratumor oxidative stress was evaluated through measurement of malondialdehyde level by HPLC, and through spectrophotometric analysis of catalytic activity of catalase and of total antioxidant capacity. Immunohistochemical analysis of tumors for CD31 expression was assessed. Intratumor activity of MMP-2 by gelatin zymography was also carried out. Our results revealed that combined therapies based on liposomal formulations exerted enhanced antitumor activities compared with combined treatment with free drugs. Sequential treatment with liposomal simvastatin and liposomal 5-fluorouracil showed the strongest antitumor activity in C26 colon carcinoma in vivo, mainly through inhibition of tumor angiogenesis. Important markers for cancer progression (Bcl-2, Bax, NF-κB, and intratumor antioxidants) showed that liposomal simvastatin might sensitize C26 cells to liposomal 5-fluorouracil treatment in both regimens tested. The outcome of simultaneous treatment with liposomal formulations was superior to sequential treatment with both liposomal types as the invasive capacity of C26 tumors was strongly increased after the latest treatment. The antitumor efficacy of combined therapy in C26 colon carcinoma might be linked to the restorative effects on proteins balance involved in tumor angiogenesis. K E Y W O R D S 5-fluorouracil, combined therapy, liposomes, resistance, simvastatin | 1345 LUPUT eT aL. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Luput L, Sesarman A, Porfire A, et al. Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5-fluorouracil in vivo.

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“…Curcumin and tumor neoangiogenesis. The growth of a solid tumor depends on tumor neovascularization (45). Angiogenic factors such as VEGF, hypoxia-inducible factor-1α, angiopoietin-1 and -2 and interleukin-2, -8 and -17 are closely associated with tumor neovascularization (46,47).…”

Section: Curcumin and Tumor Proliferation Previous Studies Havementioning

confidence: 99%

The roles of curcumin in regulating the tumor immunosuppressive microenvironment (Review)

et al. 2020

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Cancer is a harmful threat to human health. In addition to surgery, a variety of anticancer drugs are increasingly used in cancer therapy; however, despite the developments in multimodality treatment, the morbidity and mortality of patients with cancer patients are on the increase. The tumor-specific immunosuppressive microenvironment serves an important function in tumor tolerance and escape from immune surveillance leading to tumor progression. Therefore, identifying new drugs or foods that can enhance the tumor immune response is critical to develop improved cancer prevention methods and treatment. Curcumin, a polyphenolic compound extracted from ginger, has been shown to effectively inhibit tumor growth, proliferation, invasion, metastasis and angiogenesis in a variety of tumors. Recent studies have also indicated that curcumin can modulate the tumor immune response and remodel the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy of cancer. In this review, a brief introduction to the effects of curcumin on the tumor immune response and tumor immune microenvironment is provided and recent clinical trials investigating the potential of curcumin in cancer therapy are discussed.

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Trends and Challenges in Tumor Anti-Angiogenic Therapies

Cited by 171 publications

References 293 publications

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Insights into the Regulation of Tumor Angiogenesis by Micro-RNAs

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5‐fluorouracil in vivo

The roles of curcumin in regulating the tumor immunosuppressive microenvironment (Review)

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