Table 1.

Strategies to target platelet-tumor interaction for chemotherapy.

Agent	TCIPA	Cancer risk/metastasis	Bleeding	References
Classical antiplatelet drug
Aspirin	Inhibit TCIPA in vitro and in vivo	Inhibit metastasis in vivo	Increased gastrointestinal bleeding	(26, 29, 30, 169–175)
		Cancer preventive effect in human subjects (controversial in head and neck cancer)
		Reduce metastasis in cancer patients
P2Y12 receptor antagonism
Clopidogrel	Inhibit TCIPA in mice	Inhibit tumor metastasis in mice	A long-term use can increase bleeding risk	(176–182)
		No impact on cancer motility in human colorectal, breast, and prostate cancer patients
Ticagrelor	Inhibit TCIPA	Increase cancer risks in human	More major bleeding compared to clopidogrel in patients with acute coronary syndrome	(180, 183–185)
GPVI antagonism
Anti-GPVI mAb (JAQ1)	Inhibit TCIPA	Inhibit cancer cell extravasation in vitro	No impact on bleeding time	(129, 186–188)
		Inhibit metastasis in mice
		Induce intratumoral hemorrhage and accumulation of co-administrated anticancer drugs in mice
Revacept	Inhibit TCIPA in mice and human	Inhibit EMT marker expression in vitro	No impact on bleeding time in mice and human	(189–191)
Targeting CLEC2-PDPN axis
Anti-CLEC2 mAb (2A2B10 and INU1)	Inhibit intratumoral thrombus formation in mice	Inhibit metastasis in mice	No impact on bleeding time	(68, 127, 129)
Anti-PDPN mAb (NZ-1, MS-1, and SZ-168)	Inhibit platelet aggregation in mice	Inhibit metastasis in mice		(119, 128, 192–194)
		Inhibit VET in mice
2CP	Inhibit TCIPA in mice	Inhibit metastasis in mice	No impact on bleeding time	(195)
Co-HP	Inhibit platelet aggregation	Inhibit metastasis in mice	No impact on bleeding time	(126)
		Inhibit VET in mice
Polysaccharide extracted from Artemisia argyi leaves	Inhibit TCIPA			(196)