Targeting metastatic cancer

Abstract

Despite recent therapeutic advances in cancer treatment, metastasis remains the principal cause of cancer death. Recent work has uncovered the unique biology of metastasis-initiating cells that results in tumor growth in distant organs, evasion of immune surveillance and co-option of metastatic microenvironments. Here we review recent progress that is enabling therapeutic advances in treating both micro- and macrometastases. Such insights were gained from cancer sequencing, mechanistic studies and clinical trials, including of immunotherapy. These studies reveal both the origins and nature of metastases and identify new opportunities for developing more effective strategies to target metastatic relapse and improve patient outcomes.

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Fig. 1: Steps, biological functions and cancer cell vulnerabilities in the metastasis cascade.
Fig. 2: Model of metastasis subverting normal regenerative processes.
Fig. 3: Classic and new opportunities for the treatment of metastatic cancer.

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Acknowledgements

The authors’ work in the subject area of this Review is supported by NIH grants R35CA252978 (J.M.), K08CA23021 (K.G.), P30-CA008748 (MSKCC) and the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center at MSKCC (J.M.).

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Correspondence to Karuna Ganesh or Joan Massagué.

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J.M. owns stock of Scholar Rock, Inc. J.M. is an inventor on the following patents and patent applications: Assay for anti-metastatic agents (inventors: J.M. and L. Norton; no. 7,829,066; issued 9 November 2010), S100A8/A9 as a diagnostic marker and a therapeutic agent (inventor: J.M.; no. 2,831,593; granted 30 June 2018), Inhibiting cancer metastasis (inventors: J.M. and M. Valiente Cortes; no. 3,047,039; granted 31 July 2019), Methods for treating brain metastasis (inventors: J.M., Q. Chen and A. Boire; no. 10,413,522; issued 17 September 2019), Modulating permeability of the blood cerebrospinal fluid barrier (inventors: J.M. and A. A. Boire; application no. PCT/US2016/062880; published 18 November 2016). K.G. and J.M. are inventors on the following patent application: Treating metastatic cancer and model systems for metastatic disease (inventors: J.M., M. Valiente Cortes and K.G.; application no. PCT/US2017/045145; published 2 August 2017).

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Ganesh, K., Massagué, J. Targeting metastatic cancer. Nat Med 27, 34–44 (2021). https://doi.org/10.1038/s41591-020-01195-4

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