Cancer combination therapies by angiogenesis inhibitors; a comprehensive review

doi:10.1186/s12964-022-00838-y

Review

. 2022 Apr 7;20(1):49.

doi: 10.1186/s12964-022-00838-y.

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review

Mohammad Javed Ansari¹, Dmitry Bokov^{2

3}, Alexander Markov^{4

5}, Abduladheem Turki Jalil^{6

7

8}, Mohammed Nader Shalaby⁹, Wanich Suksatan¹⁰, Supat Chupradit¹¹, Hasan S Al-Ghamdi¹², Navid Shomali¹³, Amir Zamani¹⁴, Ali Mohammadi¹⁵, Mehdi Dadashpour¹⁶

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia.
² Institute of Pharmacy, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, Moscow, 119991, Russian Federation.
³ Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr., Moscow, 109240, Russian Federation.
⁴ Tyumen State Medical University, Tyumen, Russian Federation.
⁵ Industrial University, Tyumen, Russian Federation.
⁶ Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, 230023, Grodno, Belarus.
⁷ College of Technical Engineering, The Islamic University, Najaf, Iraq.
⁸ Department of Dentistry, Kut University College, Kut, Wasit, 52001, Iraq.
⁹ Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Ismailia, Egypt.
¹⁰ Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.
¹¹ Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
¹² Internal Medicine Department, Division of Dermatology, Albaha University, Al Bahah, Kingdom of Saudi Arabia.
¹³ Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran.
¹⁴ Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁵ Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran.
¹⁶ Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. dadashpourm@semums.ac.ir.

PMID: 35392964
PMCID: PMC8991477
DOI: 10.1186/s12964-022-00838-y

Review

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review

Mohammad Javed Ansari et al. Cell Commun Signal. 2022.

. 2022 Apr 7;20(1):49.

doi: 10.1186/s12964-022-00838-y.

Authors

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia.
² Institute of Pharmacy, Sechenov First Moscow State Medical University, 8 Trubetskaya St., bldg. 2, Moscow, 119991, Russian Federation.
³ Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, 2/14 Ustyinsky pr., Moscow, 109240, Russian Federation.
⁴ Tyumen State Medical University, Tyumen, Russian Federation.
⁵ Industrial University, Tyumen, Russian Federation.
⁶ Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, 230023, Grodno, Belarus.
⁷ College of Technical Engineering, The Islamic University, Najaf, Iraq.
⁸ Department of Dentistry, Kut University College, Kut, Wasit, 52001, Iraq.
⁹ Biological Sciences and Sports Health Department, Faculty of Physical Education, Suez Canal University, Ismailia, Egypt.
¹⁰ Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.
¹¹ Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
¹² Internal Medicine Department, Division of Dermatology, Albaha University, Al Bahah, Kingdom of Saudi Arabia.
¹³ Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran.
¹⁴ Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁵ Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran.
¹⁶ Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. dadashpourm@semums.ac.ir.

PMID: 35392964
PMCID: PMC8991477
DOI: 10.1186/s12964-022-00838-y

Abstract

Abnormal vasculature is one of the most conspicuous traits of tumor tissue, largely contributing to tumor immune evasion. The deregulation mainly arises from the potentiated pro-angiogenic factors secretion and can also target immune cells' biological events, such as migration and activation. Owing to this fact, angiogenesis blockade therapy was established to fight cancer by eliminating the nutrient and oxygen supply to the malignant cells by impairing the vascular network. Given the dominant role of vascular-endothelium growth factor (VEGF) in the angiogenesis process, the well-known anti-angiogenic agents mainly depend on the targeting of its actions. However, cancer cells mainly show resistance to anti-angiogenic agents by several mechanisms, and also potentiated local invasiveness and also distant metastasis have been observed following their administration. Herein, we will focus on clinical developments of angiogenesis blockade therapy, more particular, in combination with other conventional treatments, such as immunotherapy, chemoradiotherapy, targeted therapy, and also cancer vaccines. Video abstract.

Keywords: Angiogenesis; Anti-angiogenic agents; Combination therapy; Resistance; Tumor.

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Conflict of interest statement

There is no competing interests.

Figures

**Fig. 1**
The central role of VEGF in tumor angiogenesis. The VEGF induces angiogenesis in tumor cells following interaction with responding receptor, VEGFR2, on tumor cells and subsequently by activating various signaling axes. In contrast, targeting VEGF/VEGFR2 using TKI or monoclonal anti-body could be applied to fence tumor angiogenesis and development

**Fig. 2**
The contrast effects of immune cells found in TME on tumor progress. While TH2 and M2 macrophages convince tumor angiogenesis, TH1 and M1 macrophage suppress tumor angiogenesis by secreting a diversity of cytokines

**Fig. 3**
Clinical trials based on cancer therapy by anti-angiogenic agents registered in ClinicalTrials.gov (October 2021). The schematic exemplifies clinical trials utilizing anti-angiogenic agents depending on the study status (A), study phase (B), study location (C), and condition (D) in cancer patients

See this image and copyright information in PMC

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References

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[1] Folkman J. Angiogenesis. Annu Rev Med. 2006;57:1–18. - PubMed

[2] Folkman J. Angiogenesis. Annu Rev Med. 2006;57:1–18. - PubMed

[3] Senger DR, Davis GE. Angiogenesis. Cold Spring Harb Perspect Biol. 2011;3(8):a005090. - PMC - PubMed

[4] Senger DR, Davis GE. Angiogenesis. Cold Spring Harb Perspect Biol. 2011;3(8):a005090. - PMC - PubMed

[5] Aguilar-Cazares D, Chavez-Dominguez R, Carlos-Reyes A, Lopez-Camarillo C, Hernadez de la Cruz ON, Lopez-Gonzalez JS. Contribution of angiogenesis to inflammation and cancer. Front Oncol. 2019;9:1399. - PMC - PubMed

[6] Aguilar-Cazares D, Chavez-Dominguez R, Carlos-Reyes A, Lopez-Camarillo C, Hernadez de la Cruz ON, Lopez-Gonzalez JS. Contribution of angiogenesis to inflammation and cancer. Front Oncol. 2019;9:1399. - PMC - PubMed

[7] Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358(19):2039–2049. - PMC - PubMed

[8] Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008;358(19):2039–2049. - PMC - PubMed

[9] Reinmuth N, Parikh AA, Ahmad SA, Liu W, Stoeltzing O, Fan F, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Microsc Res Tech. 2003;60(2):199–207. - PubMed

[10] Reinmuth N, Parikh AA, Ahmad SA, Liu W, Stoeltzing O, Fan F, et al. Biology of angiogenesis in tumors of the gastrointestinal tract. Microsc Res Tech. 2003;60(2):199–207. - PubMed

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Cancer combination therapies by angiogenesis inhibitors; a comprehensive review

Affiliations

Cancer combination therapies by angiogenesis inhibitors; a comprehensive review

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Conflict of interest statement

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