IGF-1 is a potent mitogen of major importance in the mammary gland. IGF-1 binding to the cognate receptor, IGF-1R, triggers a signaling cascade leading to proliferative and anti-apoptotic events. Although many of the relevant molecular pathways and intracellular cascades remain to be elucidated, a growing body of evidence points to the important role of the IGF-1 system in breast cancer development, progression and metastasis. IGF-1 is a point of convergence for major signaling pathways implicated in breast cancer growth. In this review, we provide an overview and concise update on the function and regulation of IGF-1 as well as the role it plays in breast malignancies.

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Highlights d The molecular profile of RMC distinguishes it from other renal malignancies d RMC harbors a high number of focal chromosomal alterations d RMC has a distinct immune profile characterized by upregulation of cGAS-STING d DNA replication stress is a hallmark of RMC that can be therapeutically targeted

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