Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?

Abstract

The association between coagulation and cancer development has been observed for centuries. However, the connection between inflammation and malignancy is also well-recognized. The plethora of evidence indicates that among multiple hemostasis components, platelets play major roles in cancer progression by providing surface and granular contents for several interactions as well as behaving like immune cells. Therefore, the anticancer potential of anti-platelet therapy has been intensively investigated for many years. Anti-platelet agents may prevent cancer, decrease tumor growth, and metastatic potential, as well as improve survival of cancer patients. On the other hand, there are suggestions that antiplatelet treatment may promote solid tumor development in a phenomenon described as “cancers follow bleeding.” The controversies around antiplatelet agents justify insight into the subject to establish what, if any, role platelet-directed therapy has in the continuum of anticancer management.

Functional significance of the platelet immune receptors GPVI and CLEC-2

“…Platelets play a key role in tumor growth and metastasis by supporting blood and lymphatic vessel formation and aiding cancer cells in evading the immune system and metastasizing (135,136). Moreover, tumoral activation of platelets can lead to pathological thrombosis and thromboembolism that further complicate treatment (137).…”

Podoplanin: An emerging cancer biomarker and therapeutic target

“…[28][29][30][31][32][33][34] Thus, PDPN-CLEC-2 interaction offers a unique opportunity to develop anticancer strategies. [35][36][37] Antibodies can be utilized to disrupt PDPN-CLEC-2 interaction. 36,38 For example, the NZ-1 antibody, its derivatives (eg NZ-8, Phe116, Arg118 and Arg157) to inhibit its binding to PDPN, as shown in Figure 1.…”

Unexpected effects of long-term treatment with acetylsalicylic acid on late phase of pulmonary metastasis in murine model of orthotopic breast cancer

“…Acetylsalicylic acid (ASA) has been intensively studied over the last few decades with respect to its anti-metastatic effects. While at high doses ASA inhibits both isoforms of cyclooxygenase (COX-1 and COX-2) and has anti-proliferative/pro-apoptotic effects with respect to cancer cells, anti-metastatic effects of lower doses of ASA (�100 mg�kg -1 per day in humans equivalent to �15 mg�kg -1 in mice [1]) are attributed to the inhibition of COX-1 and thromboxane A 2 (TXA 2 ) synthesis by platelets [2]. Indeed, a vast number of platelet-dependent mechanisms involved in cancer progression and metastasis have been identified [3].…”