Many types of viruses directly or indirectly target the vascular endothelial growth factor (VEGF) system, which is a central regulator of vasculogenesis and angiogenesis in physiological homeostasis, causing diverse pathologies. Other viruses have been developed into effective therapeutic tools for VEGF modulation in conditions such as cancer and eye diseases. Some viruses may alter the levels of VEGF in the pathogenesis of respiratory syndromes, or they may encode VEGF-like factors, promoting vascular disruption and angiogenesis to enable viruses’ systemic spread. Oncogenic viruses may express interactive factors that perturb VEGF’s functional levels or downstream signaling, which increases the neovascularization and metastasis of tumors. Furthermore, many viruses are being developed as therapeutic vectors for vascular pathologies in clinical trials. Major examples are those viral vectors that inhibit the role of VEGF in the neovascularization required for cancer progression; this is achieved through the induction of immune responses, by exposing specific peptides that block signaling or by expressing anti-VEGF and anti-VEGF receptor-neutralizing antibodies. Other viruses have been engineered into effective pro- or anti-angiogenesis multitarget vectors for neovascular eye diseases, paving the way for therapies with improved safety and minimal side effects. This article critically reviews the large body of literature on these issues, highlighting those contributions that describe the molecular mechanisms, thus expanding our understanding of the VEGF–virus interactions in disease and therapy. This could facilitate the clinical use of therapeutic virus vectors in precision medicine for the VEGF system.

We previously established that Multifrequency Electromagnetic Pulse (MEMP) treatment selectively eradicates tumorigenic cells in vitro. While this treatment proved safe in mice and prevented tumor formation by pre-treated cells, its efficacy against established tumors remained unknown. Here we evaluate the therapeutic effect of two different systemic MEMP treatment regimens (30 Hz, >2 T) on syngeneic MC38 colon adenocarcinoma es-tablished subcutaneously in C57BL/6 mice. The impact of MEMP on anti-tumor immune infiltration (CD4, CD8, CD68) responses, as well as oxidative stress (HO-1, MDA), and DNA damage (γH2AX), cell biology markers, were analyzed by immunohistochemistry. The MEMP regimes significantly reduced the growth of the xenografted tumors leading to an apparent regression in a small subset of animals, and extended survival without af-fecting animal welfare. Of note, mice that achieved complete tumor regression mounted a protective immune response, demonstrating robust resistance to a subsequent tumor re-challenge, indicative of immunological memory. Importantly, the quantitative penetra-tion of immune effectors CD68+ cells into tumors suggests the involvement of a strong, macrophage-mediated anti-tumor response, although the ultimate mechanisms driving the MEMP effects in vivo deserve further research. These findings place MEMP as a prom-ising anti-cancer treatment and a strong candidate procedure for combination with other systemic immunotherapies.