Inflammation; Translational study; Radiotherapy; Metastasis; Cancer
Nowak-Sliwinska Patrycja, Alitalo Kari, Allen Elizabeth, Anisimov Andrey, Aplin Alfred C., Auerbach Robert, Augustin Hellmut G., Bates David O., van Beijnum Judy R., Bender R. Hugh F., Bergers Gabriele, Bikfalvi Andreas, Bischoff Joyce, Böck Barbara C., Brooks Peter C., Bussolino Federico, Cakir Bertan, Carmeliet Peter, Castranova Daniel, Cimpean Anca M., Cleaver Ondine, Coukos George, Davis George E., De Palma Michele, et al. (2018), Consensus guidelines for the use and interpretation of angiogenesis assays, in Angiogenesis
Secondini Chiara, Coquoz Oriana, Spagnuolo Lorenzo, Spinetti Thibaud, Peyvandi Sanam, Ciarloni Laura, Botta Francesca, Bourquin Carole, Rüegg Curzio (2017), Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade, in OncoImmunology
, 6(6), e1316437-e1316437.
Huang Yu-Ting, Lan Qiang, Lorusso Girieca, Duffey Nathalie, Rüegg Curzio (2017), The matricellular protein CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and suppressing anoikis, in Oncotarget
, 8(6), 9200-9215.
Spinetti Thibaud, Spagnuolo Lorenzo, Mottas Inès, Secondini Chiara, Treinies Marina, Rüegg Curzio, Hotz Christian, Bourquin Carole (2016), TLR7-based cancer immunotherapy decreases intratumoral myeloid-derived suppressor cells and blocks their immunosuppressive function, in OncoImmunology
, 5(11), e1230578-e1230578.
Mammography screening and adjuvant treatments after surgery (i.e. radiotherapy, hormonotherapy, targeted therapies and chemotherapy) significantly contributed to the reduction in breast cancer mortality observed over the past 30 years. In spite of this success, however, breast cancer remains the leading cause of cancer-related mortality for women in Europe. Mortality is due to metastases formation and the concomitant emergence of resistance to therapy. Thus, a significant decrease in breast cancer mortality can only be achieved by improving early detection and metastasis prevention/treatment. Adjuvant radiotherapy is a standard therapeutic modality in localized breast cancer and improves overall survival by approx. 30%. Radiotherapy has been classically considered to exert its effect by directly killing tumor cells. Others and we demonstrated that radiotherapy-induced modifications of the tumor microenvironment and the host also contribute to the outcome of the radiotherapy. Work from our laboratory demonstrated that radiotherapy-induced modifications of the tumor microenvironment and of the host could either promote metastasis of relapsing tumors or inhibit metastasis of tumors resected before radiotherapy (adjuvant setting). Recent results suggest that systemic inflammatory- immune-related host events induced by local radiotherapy contribute to the adjuvant effect of radiotherapy (abscopal effects). In this project we propose to build on these observations by combining in vitro cellular and molecular biology experiments, experimental models of breast cancer radiotherapy treatment, gene expression analyses and clinical studies, to address the following questions: 1) What are the local and systemic host events contributing to the therapeutic effects of adjuvant radiotherapy? 2) What is the mechanism of CYR61, a protein we previously found expressed in tumors recurring after radiotherapy, in mediating resistance to radiotherapy and metastasis?3) Does radiotherapy reprogram gene expression of pro-metastatic myelomonocytic inflammatory cells in breast cancer patients ? We anticipate that the proposed experiments will deliver important insights into mechanisms of response and resistance to radiotherapy and on mechanisms of metastasis. Obtained results may serve as a basis for the development of novel therapies or to improve the monitoring of breast cancer patients after radiotherapy.