TY - JOUR

T1 - COLORECTAL CANCER

T2 - ANGIOGENESIS AND MATRIX METALLOPROTEINASES

AU - Maiborodin, Igor V.

AU - Fursov, Sergey A.

AU - Solovenchuk, Leonid L.

AU - Gerus, Pavel A.

AU - Sheplev, Boris V.

AU - Chernyshova, Alena L.

N1 - Colorectal cancer: angiogenesis and matrix metalloproteinases / I. V. Maiborodin, S. A. Fursov, L. L. Solovenchuk [et al.] // Siberian Journal of Oncology. – 2026. – Vol. 25, No. 2. – P. 165-174. – DOI 10.21294/1814-4861-2026-25-2-165-174. – EDN PTKNJK. This work was supported by the Russian state-funded project for ICBFM SB RAS (grant number 125012300674-9). The authors did not receive financial support from the drug manufacturers

PY - 2026

Y1 - 2026

N2 - Aim: to summarize the available literature data on the role of matrix metalloproteinases (MMPs) in angiogenesis, as well as in the development and progression of colorectal cancer (CRC). Material and Methods. A literature search was conducted in the Medline and eLIBRARY.RU databases from 1999 to the present using the keywords “angiogenesis + cancer + colon + MMP”. Results. Malignant tumors are characterized by the ability to form new vessels, invade surrounding tissues, and metastasize to distant organs, and this aggressiveness depends on the expression of proteolytic enzymes, including MMPs. In CRC, the levels of MMPs are increased in both tumor tissues and blood plasma; these enzymes are required for extracellular matrix remodelling during angiogenesis, tumor invasion and metastasis. The degree of overexpression of certain MMPs correlates with the stage of CRC, vascularization, VEGF expression and/or prognosis; however, not all researchers agree with these findings. MMPs are synthesized both by tumor cells and, more prominently, stromal cells like tumor-associated macrophages. Alterations in the function of immunocompetent and stromal cells that express and produce MMPs play a key role in both the initiation and progression of CRC. Targeting tumor-associated immunocompetent and stromal cells, their reprogramming, neutralization and/or inhibition of their trafficking may delay the growth and invasion of CRC. Inhibition of MMPs may represent one of the stages of antiangiogenic therapy. In addition to suppressing angiogenesis, certain MMP inhibitors stimulate apoptosis, suppress cell proliferation, induce cell cycle arrest, and reduce the expression of antiapoptotic genes of the Bcl family. A wide range of artificial and natural compounds and methods has been proposed as MMP inhibitors. However, despite promising experimental results, clinical trials of MMP inhibitors have been largely disappointing. There is evidence that some MMPs exert antitumor effects, and their blockade may be accompanied by tumor progression. Conclusion. A wide variety of approaches to targeting MMPs, together with the certain inconsistency of available data, may indicate the persisting dissatisfaction of researchers and clinicians with the current solutions to the problem of MMP-mediated angiogenesis in tumor tissues. This also highlights the need for continued investigation into both the effects of MMPs in CRC and the methods for controlling the activity of this enzyme group.

AB - Aim: to summarize the available literature data on the role of matrix metalloproteinases (MMPs) in angiogenesis, as well as in the development and progression of colorectal cancer (CRC). Material and Methods. A literature search was conducted in the Medline and eLIBRARY.RU databases from 1999 to the present using the keywords “angiogenesis + cancer + colon + MMP”. Results. Malignant tumors are characterized by the ability to form new vessels, invade surrounding tissues, and metastasize to distant organs, and this aggressiveness depends on the expression of proteolytic enzymes, including MMPs. In CRC, the levels of MMPs are increased in both tumor tissues and blood plasma; these enzymes are required for extracellular matrix remodelling during angiogenesis, tumor invasion and metastasis. The degree of overexpression of certain MMPs correlates with the stage of CRC, vascularization, VEGF expression and/or prognosis; however, not all researchers agree with these findings. MMPs are synthesized both by tumor cells and, more prominently, stromal cells like tumor-associated macrophages. Alterations in the function of immunocompetent and stromal cells that express and produce MMPs play a key role in both the initiation and progression of CRC. Targeting tumor-associated immunocompetent and stromal cells, their reprogramming, neutralization and/or inhibition of their trafficking may delay the growth and invasion of CRC. Inhibition of MMPs may represent one of the stages of antiangiogenic therapy. In addition to suppressing angiogenesis, certain MMP inhibitors stimulate apoptosis, suppress cell proliferation, induce cell cycle arrest, and reduce the expression of antiapoptotic genes of the Bcl family. A wide range of artificial and natural compounds and methods has been proposed as MMP inhibitors. However, despite promising experimental results, clinical trials of MMP inhibitors have been largely disappointing. There is evidence that some MMPs exert antitumor effects, and their blockade may be accompanied by tumor progression. Conclusion. A wide variety of approaches to targeting MMPs, together with the certain inconsistency of available data, may indicate the persisting dissatisfaction of researchers and clinicians with the current solutions to the problem of MMP-mediated angiogenesis in tumor tissues. This also highlights the need for continued investigation into both the effects of MMPs in CRC and the methods for controlling the activity of this enzyme group.

KW - colorectal cancer

KW - inhibitors of matrix metalloproteinases

KW - matrix metalloproteinases

KW - prognostic factors

KW - tumor angiogenesis

KW - tumor vascularization

KW - tumor-associated macrophages

KW - рак толстой кишки

KW - матриксные металлопротеиназы

KW - опухолевый ангиогенез

KW - васкуляризация опухоли

KW - туморассоциированные макрофаги

KW - ингибиторы матриксных металлопротеиназ

KW - факторы прогноза

UR - https://www.mendeley.com/catalogue/91d7984c-3dfe-3dc0-8a5a-439cb815cd88/

UR - https://www.scopus.com/pages/publications/105042643932

UR - https://www.elibrary.ru/item.asp?id=90498629

U2 - 10.21294/1814-4861-2026-25-2-165-174

DO - 10.21294/1814-4861-2026-25-2-165-174

M3 - Article

VL - 25

SP - 165

EP - 174

JO - Siberian Journal of Oncology

JF - Siberian Journal of Oncology

SN - 1814-4861

IS - 2

ER -