Publication

The selective Tie2 inhibitor rebastinib blocks recruitment and function of Tie2Hi macrophages in breast cancer and neuroendocrine pancreatic tumors

Michele De Palma, Ece Kadioglu
2017
Journal paper
Abstract

Tumor-infiltrating myeloid cells promote tumor progression by mediating angiogenesis, tumor cell intravasation and metastasis, which can offset the effects of chemotherapy, radiation, and anti-angiogenic therapy. Here, we show that the kinase switch control inhibitor rebastinib inhibits Tie2, a tyrosine kinase receptor expressed on endothelial cells and pro-tumoral Tie2-expressing macrophages in mouse models of metastatic cancer. Rebastinib reduces tumor growth and metastasis in an orthotopic mouse model of metastatic mammary carcinoma through reduction of Tie2+ myeloid cell infiltration, anti-angiogenic effects, and blockade of tumor cell intravasation mediated by perivascular Tie2(hi)/VegfA(hi) macrophages in the tumor microenvironment of metastasis (TMEM). The anti-tumor effects of rebastinib enhance the efficacy of microtubule inhibiting chemotherapeutic agents, either eribulin or paclitaxel, by reducing tumor volume, metastasis, and improving overall survival. Rebastinib inhibition of angiopoietin/Tie2 signaling impairs multiple pathways in tumor progression mediated by pro-tumoral Tie2+ macrophages, including TMEM-dependent dissemination and angiopoietin/Tie2-dependent angiogenesis. Rebastinib is a promising therapy for achieving Tie2 inhibition in cancer patients.

About this result
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
Ontological neighbourhood
Related concepts (36)
Metastatic breast cancer
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV. Metastases can occur several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise (especially in older texts).
Tumor microenvironment
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
Show more
Related publications (90)

Tumor-educated Gr1+CD11b+cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity

Nadine Fournier, Manon Bulliard, Annamaria Kauzlaric, Yu-Ting Huang, Rachel Marcone

Cancer cell plasticity contributes to therapy resistance and metastasis, which represent the main causes of cancer-related death, including in breast cancer. The tumor microenvironment drives cancer cell plasticity and metastasis, and unraveling the underl ...
Amer Soc Clinical Investigation Inc2024

Unveiling breast cancer metastasis through an advanced X-ray imaging approach

Marianne Liebi

Breast cancer is a significant global health burden, causing a substantial number of deaths. Systemic metastatic tumour cell dissemination is a major cause of poor outcomes. Understanding the mechanisms underlying metastasis is crucial for effective interv ...
Berlin2024

Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial

Elise Hélène Dumas, Fabrice André

Background Circadian rhythms regulate cellular physiology and could in fl uence the ef fi cacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). Methods 1278 p ...
Elsevier2024
Show more
Related MOOCs (5)
Introduction à l'immunologie (part 1)
Ce cours décrit les mécanismes fondamentaux du système immunitaire pour mieux comprendre les bases immunologiques dela vaccination, de la transplantation, de l’immunothérapie, de l'allergie et des mal
Show more

Graph Chatbot

Chat with Graph Search

Ask any question about EPFL courses, lectures, exercises, research, news, etc. or try the example questions below.

DISCLAIMER: The Graph Chatbot is not programmed to provide explicit or categorical answers to your questions. Rather, it transforms your questions into API requests that are distributed across the various IT services officially administered by EPFL. Its purpose is solely to collect and recommend relevant references to content that you can explore to help you answer your questions.