Macomics

Jun 25, 2024

Abstract Research into the mechanisms and manifestations of solid tumor vascularization was launched more than 50 years ago with the proposition and experimental demonstrations that angiogenesis is instrumental for tumor growth and was, therefore, a promising therapeutic target. The biological knowledge and therapeutic insights forthcoming have been remarkable, punctuated by new concepts, many of which were not foreseen in the early decades. This article presents a perspective on tumor vascularization and its therapeutic targeting but does not portray a historical timeline. Rather, we highlight eight conceptual milestones, integrating initial discoveries and recent progress and posing open questions for the future. Access options Get Nature+, our best-value online-access subscription $29.99 / 30 days $119.00 per year Additional access options: Fig. 2: Accessory cells in tumor angiogenesis. Fig. 3: Diversity of tumor vascularization: the angiogenic switch and vascular co-option. Fig. 4: Harnessing vascular–immune crosstalk for cancer therapy. References Potente, M., Gerhardt, H. & Carmeliet, P. Basic and therapeutic aspects of angiogenesis. Cell 146, 873–887 (2011). Solorzano, C. C. et al. Administration of optimal biological dose and schedule of interferon α combined with gemcitabine induces apoptosis in tumor-associated endothelial cells and reduces growth of human pancreatic carcinoma implanted orthotopically in nude mice. Clin. Cancer Res. 9, 1858–1867 (2003). Tabernero, J. et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 16, 499–508 (2015). Yang, B., Li, Y., Deng, J., Yang, H. & Sun, X. Efficacy and safety of immune checkpoint inhibitors plus recombinant human endostatin therapy as second-line treatment in advanced non-small-cell lung cancer with negative driver gene: a pilot study. Front. Oncol. 13, 1210267 (2023). Bilen, M. A. et al. Association of neutrophil-to-lymphocyte ratio with efficacy of first-line avelumab plus axitinib vs. sunitinib in patients with advanced renal cell carcinoma enrolled in the phase 3 JAVELIN Renal 101 trial. Clin. Cancer Res. 28, 738–747 (2022). Acknowledgements We note and regret that many pertinent studies were not cited owing to the limited number of references allowed for this article format. We thank K. Ouchen for redrawing our vignettes. M.D.P. acknowledges grant support from the European Research Council (ERC CoG EVOLVE-725051), the Swiss National Science Foundation (SNSF 310030-188868), the Swiss Cancer League (KLS-4505-08-2018) and Carigest SA. D.H. acknowledges grant support from the Ludwig Institute for Cancer Research. Author information Authors and Affiliations Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), Lausanne, Switzerland Michele De Palma & Douglas Hanahan Agora Cancer Research Center, Lausanne, Switzerland Michele De Palma & Douglas Hanahan Swiss Cancer Center Léman (SCCL), Lausanne, Switzerland Michele De Palma & Douglas Hanahan Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland Douglas Hanahan Douglas Hanahan Corresponding authors Competing interests None of the research results reviewed and discussed herein reflect bona fide competing interests. In the interest of full disclosure, M.D.P. has received sponsored research grants from Hoffmann La-Roche, Deciphera Pharmaceuticals, MedImmune and EVIR Therapeutics, in part to investigate angiogenesis inhibitors and immunotherapy combinations; serves on the scientific advisory boards of EVIR Therapeutics, Montis Biosciences, Macomics, Deciphera Pharmaceuticals, Light Chain Bioscience/Novimmune and Genenta; and is an inventor on patents on engineered immune cells filed by the Swiss Federal Institute of Technology in Lausanne (EPFL). D.H. has received sponsored research grants from Hoffmann La-Roche and Bristol Myers Squibb; serves on the scientific advisory boards of Pfizer Oncology, Opna Bio, 4D Molecular Therapeutics and Cellestia; and is a founder of Opna Bio, which has licensed an EPFL patent describing the RNA-binding protein FMRP as a new cancer target. 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