29 October 2019
Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, they used intravital microscopy of orthotopic sarcoma and melanoma xenografts. They demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, they targeted β1 and αVβ3/β5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with β1 or αV integrin monotargeting in invading tumors led to relapse and metastasis in 40–60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-β1/αV integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by β1/αVβ3/β5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting.
Cancer fatalities result from metastatic dissemination and therapy resistance, both processes that depend on signals from the tumor microenvironment. To identify how invasion and resistance programs cooperate, they used intravital microscopy of orthotopic sarcoma and melanoma xenografts. They demonstrate that these tumors invade collectively and that, specifically, cells within the invasion zone acquire increased resistance to radiotherapy, rapidly normalize DNA damage, and preferentially survive. Using a candidate-based approach to identify effectors of invasion-associated resistance, they targeted β1 and αVβ3/β5 integrins, essential extracellular matrix receptors in mesenchymal tumors, which mediate cancer progression and resistance. Combining radiotherapy with β1 or αV integrin monotargeting in invading tumors led to relapse and metastasis in 40–60% of the cohort, in line with recently failed clinical trials individually targeting integrins. However, when combined, anti-β1/αV integrin dual targeting achieved relapse-free radiosensitization and prevented metastatic escape. Collectively, invading cancer cells thus withstand radiotherapy and DNA damage by β1/αVβ3/β5 integrin cross-talk, but efficient radiosensitization can be achieved by multiple integrin targeting.
Related news items
![](https://www.radboudumc.nl/getmedia/ec7e3d0b-827d-4a8d-84de-7bd0744836c1/Friedl,-Peter-uitsnede.aspx?width=2822&height=1693&ext=.png&type=BlockColumn1Zoom1)
NWO open call GROOT grant for Peter Friedl
24 February 2020 Peter Friedl, theme Cancer development and immune defense, received a 300,000 EUR grant within the NWO-GROOT consortium "Active matter of cancer metastasis" to identify the mechanisms of collective metastasis in breast cancer. read more![](https://www.radboudumc.nl/getmedia/ec7e3d0b-827d-4a8d-84de-7bd0744836c1/Friedl,-Peter-uitsnede.aspx?width=2822&height=1693&ext=.png&type=BlockColumn1Zoom1)
p120-catenin-dependent collective brain infiltration by glioma cell networks
7 January 2020 Pavlo Gritsenko and Peter Friedl, theme Cancer development and immune defense, report in Nature Cell Biology, that glioma cells infiltrate the brain by a collective network mechanism, which critically depends on p120 catenin. p120 thus represents a potential target to combat glioma. read more![](https://www.radboudumc.nl/getmedia/c06d74f7-d16e-417d-9bf6-4217122b262b/NWO-vidi.aspx?width=270&height=162&ext=.png&type=BlockColumn1Zoom1)
Three VIDI grants for RIMLS researchers
24 May 2019 Matthijs Jore, Daniele Tauriello and Johannes Textor are each to receive up to 800,000 euros to develop an innovative research theme and to build up their own research group. NWO is awarding the Vidi grant as part of the Innovational Research Incentives Scheme. read more![](https://www.radboudumc.nl/getmedia/95fe9baa-00c1-4b9b-a4f9-4b7033787bcb/New-years-drinks-2019.aspx?width=855&height=513&ext=.jpg&type=BlockColumn1Zoom1)
RIMLS awards festival Twelve winners
16 January 2019 In 5 categories RIMLS young researchers received an award and bonus during the New Year's drinks. See all photo's. read more![](https://www.radboudumc.nl/getmedia/88276377-5326-43c9-b42f-69b0301205b3/THEME-Cancer-development-and-immune-defense.aspx?width=2560&height=1920&ext=.jpg&type=BlockColumn1Zoom1)
Cancer cell moves like a predator Lévy walk may be the weak spot of cancer cells
19 November 2018 In contrast to their non-metastatic counterparts, metastatic cancer cells show movement patterns that are also often employed by predators searching for prey. This was shown by an international study on movement patterns of cancer cells published in Nature Communications. read more![](https://www.radboudumc.nl/getmedia/f3c27991-48c9-455f-9572-88aa736d0512/Turbo-grants-2018.aspx?width=395&height=237&ext=.png&type=BlockColumn1Zoom1)