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Clinical implications of cancer self-seeding

Abstract

Most metastatic cancers are incurable—a fact that underscores the limitations of our existing paradigms for understanding metastasis. In this Review, we use breast cancer to explore many of the enigmas revealed by these existing paradigms. Traditionally, metastatic models describe metastasis as a unidirectional process, whereby cancer cells leave a primary tumor and unidirectionally seed metastasis in regional lymph nodes or distant sites. By contrast, recent data indicate that metastasis is a multidirectional process whereby cancer cells can seed distant sites as well as the primary tumor itself. This later process, known as 'self-seeding,' has been validated in diverse experimental models. Here, we show that the self-seeding model may answer many of the mysteries inherent to cancer metastasis. Indeed, reframing our understanding of metastasis within the self-seeding model offers new opportunities for prevention and cure of metastatic cancer.

Key Points

  • Most metastatic cancers are currently incurable; thus, existing paradigms for understanding metastasis reveal persistent enigmas

  • In breast cancer, unsolved mysteries include the similarities between pre-cancer and cancer, mammographic breast density as a risk factor, and the relationship between local control and distant recurrence

  • A new paradigm, termed 'self-seeding,' reconciles many of these enigmas

  • Self-seeding describes the multidirectional capacity of cancer cells to seed distant organs as well as self-seed a primary tumor

  • Reframing drug development and clinical investigation within a self-seeding model may be a harbinger for clinical progress in curing metastatic cancers

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Figure 1: The concept of self-seeding that explains cancer growth and metastasis.

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E. Comen and L. Norton both contributed to the writing of this manuscript. E. Comen, L. Norton and J. Massagué contributed equally to researching the data for this article, discussion of the content and reviewing and edited the manuscript before submission and during the editing process.

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Correspondence to Larry Norton.

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Comen, E., Norton, L. & Massagué, J. Clinical implications of cancer self-seeding. Nat Rev Clin Oncol 8, 369–377 (2011). https://doi.org/10.1038/nrclinonc.2011.64

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