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Cancers
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Angiogenesis and Anti-angiogenic Therapies
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Angiogenesis and Anti-angiogenic Therapies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 15486

Special Issue Editor

Dr. Madhuri Wadehra

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Guest Editor
Department of Pathology and Lab Medicine, DGSOM at UCLA, Los Angeles, USA
Interests: antibody therapies; tumour vascularisation; tetraspan proteins

Special Issue Information

Dear colleagues,

As Judah Folkman proposed 40 years ago, the sprouting of new vessels out of existing ones was considered as an exclusive way of tumor vascularisation. In neoplastic tissue, this process is multidimensionally regulated by tumor cells and a variety of stromal cells. While many growth factors and mechanisms have been unraveled, new complexities are constantly being discovered, such as with the recruitment of endothelial progenitor cells, vessel co-option, vasculogenic mimicry, and lymphangiogenesis to tumor growth, to name a few. Nonetheless, targeting tumor angiogenesis is a fast-growing domain in cancer therapeutics. Although anti-tumor targeting strategies have proven to be more complex than initially thought, several anti-angiogenics have proven successful for select tumor types. 

In this Cancers review, we seek to obtain high-quality reviews on various aspects of the mechanism of tumor neoangiogenesis as well as successes and failures associated with anti-angiogenetics. Each review may focus broadly on the processes associated with tumor angiogenesis or take a more focused approach to discuss processes unique to a particular tumor type.

We would be happy to discuss in more detail and hope that you will consider submitting a review.

Dr. Madhuri Wadehra
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

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12 pages, 1127 KiB  
Article
Afatinib Treatment Alone or with Bevacizumab in a Real-World Cohort of Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Mutation
by Chih-Hsi Scott Kuo, Tzu-Hsuan Chiu, Pi-Hung Tung, Chi-Hsien Huang, Jia-Shiuan Ju, Allen Chung-Cheng Huang, Chin-Chou Wang, Ho-Wen Ko, Ping-Chih Hsu, Yueh-Fu Fang, Yi-Ke Guo and Cheng-Ta Yang
Cancers 2022, 14(2), 316; https://doi.org/10.3390/cancers14020316 - 9 Jan 2022
Cited by 5 | Viewed by 1956
Abstract
Background: Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor (EGFR) mutation remains insufficiently reported. Methods: A total of 405 advanced NSCLC patients with sensitizing-EGFR mutation receiving first-line single-agent [...] Read more.
Background: Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor (EGFR) mutation remains insufficiently reported. Methods: A total of 405 advanced NSCLC patients with sensitizing-EGFR mutation receiving first-line single-agent afatinib or with bevacizumab were grouped and propensity score-matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analyzed. Results: In the original cohort, 367 (90.6%) patients received afatinib treatment alone and 38 (9.4%) patients received afatinib plus bevacizumab. Patients who received bevacizumab combination were significantly younger (54.6 ± 10.9 vs. 63.9 ± 11.5; p < 0.001) compared to the afatinib alone group. After propensity score matching, the afatinib alone and afatinib plus bevacizumab groups contained 118 and 34 patients, respectively. A non-significantly higher objective response was noted in the afatinib plus bevacizumab group (82.4% vs. 67.8%; p = 0.133). In the propensity score-matched cohort, a bevacizumab add-on offered no increased PFS (16.1 vs. 15.0 months; p = 0.500), risk reduction of progression (HR 0.85 [95% CI, 0.52–1.40]; p = 0.528), OS benefit (32.1 vs. 42.0 months; p = 0.700), nor risk reduction of death (HR 0.85 [95% CI, 0.42–1.74] p = 0.660) compared to the single-agent afatinib. The secondary T790M rate in afatinib plus bevacizumab and afatinib alone groups was similar (56.3% vs. 49.4%, p = 0.794). Multivariate analysis demonstrated that EGFR L858R (OR 0.51 [95% CI, 0.26–0.97]; p = 0.044), EGFR uncommon mutation (OR 0.14 [95% CI, 0.02–0.64]; p = 0.021), and PFS longer than 12 months (OR 2.71 [95% CI, 1.39–5.41]; p = 0.004) were independent predictors of secondary T790M positivity. Conclusion: Bevacizumab treatment showed moderate efficacy in real-world, afatinib-treated NSCLC patients with EGFR-sensitizing mutation. Full article
(This article belongs to the Special Issue Angiogenesis and Anti-angiogenic Therapies)
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Review

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14 pages, 695 KiB  
Review
Exploring the Past, Present, and Future of Anti-Angiogenic Therapy in Glioblastoma
by Ashley B. Zhang, Khashayar Mozaffari, Brian Aguirre, Victor Li, Rohan Kubba, Nilay C. Desai, Darren Wei, Isaac Yang and Madhuri Wadehra
Cancers 2023, 15(3), 830; https://doi.org/10.3390/cancers15030830 - 29 Jan 2023
Cited by 9 | Viewed by 2681
Abstract
Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding [...] Read more.
Glioblastoma, a WHO grade IV astrocytoma, constitutes approximately half of malignant tumors of the central nervous system. Despite technological advancements and aggressive multimodal treatment, prognosis remains dismal. The highly vascularized nature of glioblastoma enables the tumor cells to grow and invade the surrounding tissue, and vascular endothelial growth factor-A (VEGF-A) is a critical mediator of this process. Therefore, over the past decade, angiogenesis, and more specifically, the VEGF signaling pathway, has emerged as a therapeutic target for glioblastoma therapy. This led to the FDA approval of bevacizumab, a monoclonal antibody designed against VEGF-A, for treatment of recurrent glioblastoma. Despite the promising preclinical data and its theoretical effectiveness, bevacizumab has failed to improve patients’ overall survival. Furthermore, several other anti-angiogenic agents that target the VEGF signaling pathway have also not demonstrated survival improvement. This suggests the presence of other compensatory angiogenic signaling pathways that surpass the anti-angiogenic effects of these agents and facilitate vascularization despite ongoing VEGF signaling inhibition. Herein, we review the current state of anti-angiogenic agents, discuss potential mechanisms of anti-angiogenic resistance, and suggest potential avenues to increase the efficacy of this therapeutic approach. Full article
(This article belongs to the Special Issue Angiogenesis and Anti-angiogenic Therapies)
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22 pages, 1737 KiB  
Review
Frontiers in Anti-Cancer Drug Discovery: Challenges and Perspectives of Metformin as Anti-Angiogenic Add-On Therapy in Glioblastoma
by Laura Guarnaccia, Giovanni Marfia, Matteo Maria Masseroli, Stefania Elena Navone, Melissa Balsamo, Manuela Caroli, Silvia Valtorta, Rosa Maria Moresco, Rolando Campanella, Emanuele Garzia, Laura Riboni and Marco Locatelli
Cancers 2022, 14(1), 112; https://doi.org/10.3390/cancers14010112 - 27 Dec 2021
Cited by 14 | Viewed by 3275
Abstract
Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its [...] Read more.
Glioblastoma is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. Glioblastoma shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), has demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including glioblastoma. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss metformin’s potential antitumoral effects on glioblastoma, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of glioblastoma patients. Full article
(This article belongs to the Special Issue Angiogenesis and Anti-angiogenic Therapies)
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28 pages, 3083 KiB  
Review
Biologically-Based Mathematical Modeling of Tumor Vasculature and Angiogenesis via Time-Resolved Imaging Data
by David A. Hormuth II, Caleb M. Phillips, Chengyue Wu, Ernesto A. B. F. Lima, Guillermo Lorenzo, Prashant K. Jha, Angela M. Jarrett, J. Tinsley Oden and Thomas E. Yankeelov
Cancers 2021, 13(12), 3008; https://doi.org/10.3390/cancers13123008 - 16 Jun 2021
Cited by 32 | Viewed by 6628
Abstract
Tumor-associated vasculature is responsible for the delivery of nutrients, removal of waste, and allowing growth beyond 2–3 mm3. Additionally, the vascular network, which is changing in both space and time, fundamentally influences tumor response to both systemic and radiation therapy. Thus, [...] Read more.
Tumor-associated vasculature is responsible for the delivery of nutrients, removal of waste, and allowing growth beyond 2–3 mm3. Additionally, the vascular network, which is changing in both space and time, fundamentally influences tumor response to both systemic and radiation therapy. Thus, a robust understanding of vascular dynamics is necessary to accurately predict tumor growth, as well as establish optimal treatment protocols to achieve optimal tumor control. Such a goal requires the intimate integration of both theory and experiment. Quantitative and time-resolved imaging methods have emerged as technologies able to visualize and characterize tumor vascular properties before and during therapy at the tissue and cell scale. Parallel to, but separate from those developments, mathematical modeling techniques have been developed to enable in silico investigations into theoretical tumor and vascular dynamics. In particular, recent efforts have sought to integrate both theory and experiment to enable data-driven mathematical modeling. Such mathematical models are calibrated by data obtained from individual tumor-vascular systems to predict future vascular growth, delivery of systemic agents, and response to radiotherapy. In this review, we discuss experimental techniques for visualizing and quantifying vascular dynamics including magnetic resonance imaging, microfluidic devices, and confocal microscopy. We then focus on the integration of these experimental measures with biologically based mathematical models to generate testable predictions. Full article
(This article belongs to the Special Issue Angiogenesis and Anti-angiogenic Therapies)
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