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The dynamic role of platelets in cancer progression and their therapeutic implications

Nature Reviews Cancer volume 24, pages 72–87 (2024)Cite this article

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Abstract

Systemic antiplatelet treatment represents a promising option to improve the therapeutic outcomes and therapeutic efficacy of chemotherapy and immunotherapy due to the critical contribution of platelets to tumour progression. However, until recently, targeting platelets as a cancer therapeutic has been hampered by the elevated risk of haemorrhagic and thrombocytopenic (low platelet count) complications owing to the lack of specificity for tumour-associated platelets. Recent work has advanced our understanding of the molecular mechanisms responsible for the contribution of platelets to tumour progression and metastasis. This has led to the identification of the biological changes in platelets in the presence of tumours, the complex interactions between platelets and tumour cells during tumour progression, and the effects of platelets on antitumour therapeutic response. In this Review, we present a detailed picture of the dynamic roles of platelets in tumour development and progression as well as their use in diagnosis, prognosis and monitoring response to therapy. We also provide our view on how to overcome challenges faced by the development of precise antiplatelet strategies for safe and efficient clinical cancer therapy.

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Fig. 1: Tumour cells alter platelet biology.
Fig. 2: Direct and indirect platelet–tumour cell interactions promote platelet education and activation.
Fig. 3: The contribution of platelets to promoting tumour growth and progression.
Fig. 4: Anticancer strategies involve targeting platelet–tumour cell interactions or utilizing engineered platelets or platelet-like carriers for drug delivery.

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Acknowledgements

The authors want to express special thanks to T. Zhou, Westlake University, for providing helpful suggestions for our draft revision. This work was supported by grants from the Beijing Distinguished Young Scientist programme (JQ20037 to S.L.), CAS Interdisciplinary Innovation Team (JCTD-2020-04 to S.L.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000 to G.N.), CAS Project for Young Scientists in Basic Research (No. YSBR-036 to S.L.), the Key Area R&D Program of Guangdong Province (2020B0101020004 to S.L.), the National Basic Research Plan of China (2018YFA0208900 to G.N.), and the National Natural Science Foundation of China (31730032 to G.N., 31820103004 to G.N.).

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  1. These authors contributed equally: Suping Li, Zefang Lu.

Authors and Affiliations

  1. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China

    Suping Li, Zefang Lu, Suying Wu, Tianjiao Chu, Bozhao Li, Feilong Qi, Yuliang Zhao & Guangjun Nie

  2. Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, China

    Suping Li, Zefang Lu, Suying Wu, Feilong Qi, Yuliang Zhao & Guangjun Nie

  3. College of Pharmaceutical Science, Jilin University, Changchun, China

    Tianjiao Chu

  4. Department of Chemistry, Tsinghua University, Beijing, China

    Feilong Qi

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Contributions

G.N., S.L., Z.L., S.W., T.C., B.L. and F.Q. researched the data for this article. All authors contributed substantially to the discussion of content. S.L., G.N. and Z.L. wrote the article. G.N., S.L., Z.L. and Y.Z. reviewed and edited the manuscript before submission.

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Glossary

Area under the curve

(AUC). A measure of how well a parameter can distinguish normal groups from diseased groups; the greater the AUC, the better the parameter.

Blood shear stress

In the circulation, cancer cells are subjected to the tangential or frictional forces of the blood flow, causing mechanical stress and subsequent damage to circulating tumour cells.

Haemocyte

Haemocytes are cells that circulate in the blood and are generated via haematopoiesis; they include red blood cells, leukocytes and platelets.

Haemostasis

The physiological process of blood clot formation at the site of vessel injury while maintaining normal blood flow elsewhere.

Paraneoplastic

A syndrome that occurs when the body has a systemic reaction to a cancerous tumour.

Platelet releasates

Soluble factors, small molecules and vesicles secreted by platelets when activated.

Soluble N-ethylmaleimide factor attachment protein receptors

(SNAREs). Essential proteins involved in mediating protein secretion by membrane fusion of storage granules within cells.

Venous thromboembolism

(VTE). When a blood clot forms in the veins, including deep vein thrombosis and pulmonary embolism.

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Li, S., Lu, Z., Wu, S. et al. The dynamic role of platelets in cancer progression and their therapeutic implications. Nat Rev Cancer 24, 72–87 (2024). https://doi.org/10.1038/s41568-023-00639-6

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