Page 47 - Rappaport Institute Magazine 2024

CELL BIOLOGY AND CANCER SCIENCE
44-45
Host response to anti-cancer drugs
One of the major obstacles in clinical oncology is that tumors may often relapse, resist therapy and sometimes even spread despite an initial successful treatment. While tumor relapse is mainly attributed to tumor cell intrinsic resistance, we have pioneered the idea that host effects generated in response to therapy are substantially involved in tumor resistance and could even lead to metastasis spread. We termed this phenomenon as “host response to anti-cancer therapy”. We demonstrated that almost any type of anti-cancer treatment induces such host effects which contribute to tumor re-growth and spread. Our lab studies the possible cross-talks between tumor and host cells at the tumor microenvironment. We demonstrate how host cells exposed to anti-cancer drugs can change the tumor microenvironment to the tumor advantage, and how therapy-educated host cells can dictate a pro-tumorigenic tumor microenvironment, even in naïve (untreated) tumors. More recently the lab focuses on how therapy contributes to changes in the extracellular matrix. Based on such studies we also develop possible new therapeutic strategies which primarily inhibit host pro-tumorigenic response effects as well as new ways to predict clinical outcomes therefore effectively advancing personalized treatment.
Selected Publications
ˆ Benguigui M, Cooper TJ*, Kalkar P, Schif-Zuck S, Halaban R, Bacchiocchi A, Kamer I, Deo A, Manobla B, Menachem R, Haj-Shomaly J, Vorontsova A, Raviv Z, Buxbaum C, Christopoulos P, Bar J, Lotem M, Sznol M, Ariel A, Shen-Orr SS, Shaked Y*. Interferon- stimulated neutrophils as a predictor of immunotherapy response. Cancer Cell 2024, 4:S1535-6108(23)00433-6. (Highlighted in Nature Reviews Immunology). [*co- corresponding authors].
ˆ Vorontsova, A., J. Cooper, T., Haj-Shomaly, J., Benguigui, M., Levin, S., Manobla,
B., Menachem, R., Timaner, M., Raviv, R., Shaked, Y. Chemotherapy-induced tumor immunogenicity is mediated in part by megakaryocyte-erythroid progenitors. Oncogene 2023; 42(10):771-781.
ˆ Haj-Shomaly, J., Vorontsova, A., Barenholz-Cohen, T., Levi-Galibov, O., Devarasetty, M., Timaner, M., Raviv, Z., Cooper, TJ., Soker, S., Hasson, P., Weihs, D., Scherz- Shouval, R., Shaked, Y. T cells promote metastasis by regulating extracellular matrix remodeling following chemotherapy. Cancer Research 2022, 15;82(2):278-291. (cover and editorial).
ˆ Shaked, Y. The protumorigenic host response to cancer therapy. Nature Reviews Cancer 2019(12):667-685.
ˆ Shaked, Y. Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects. Nature Reviews Clin. Onco. 2016; 13(10):611-26.
Grants and Awards
2017 – 2022 ERC starting grant Neuronal regulation of immunity 2023 – 2028 ERC consolidator grant Neuronal regulation of the fascia
yshaked@technion.ac.il
Yuval Shaked Lab
Yuval Shaked, PhD Professor of Cancer Biology
PhD, 2005 – The Hebrew University of Jerusalem, Isarel
Scanned electron microscopy of collagen fibers in the lungs of mice bearing breast cancer. The changes in the collagen fibers after treatment suggest that the lungs undergo ECM remodeling which support cancer cell binding.