Metastasis: Recent Discoveries and Novel Perioperative Treatment Strategies with Particular Interest in the Hemostatic Compound Desmopressin

Abstract

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

MicroRNA‑154/ADAM9 axis inhibits the proliferation, migration and invasion of breast cancer cells

“…At present, the primary methodology for breast cancer therapy is resective surgery followed by hormonal therapy, chemotherapy, radiotherapy and/or biological therapy (8,9). Although great progress has been made in the earlier diagnosis and systemic therapy of patients with breast cancer in recent years, recurrence or distant metastasis continue to present major barriers to the successful treatment of breast cancer (10,11). Therefore, fully understanding the molecular mechanisms underlying the progression of breast cancer may be critical for the development of effective therapeutic strategies against breast cancer.…”

Response

“…Perioperative administration of DDAVP at high doses of 1 μg/kg prolonged disease-free and overall survival. An extended trial recently confirmed these results, showing a reduced incidence of local relapses and lung metastasis in treated animals and a particular survival benefit in cases with more aggressive carcinoma (6). It is likely that DDAVP infusion not only inhibits perioperative metastastic events but also combats micrometastases that occurred before surgery.…”

“…However, we agree with Dr Alonso's proposal that raising the levels of VWF within the blood vessels at the premetastatic sites by a pharmacological intervention using desmopressin (DDAVP) may be another strategy. Compared with the development and clinical trials of ADAM28-selective inhibitors, the treatment using DDAVP may have several advantages: First, DDAVP has been clinically used without adverse effects for patients with von Willebrand disease or hemophilia A, and thus it appears to be a very safe drug (5,6). Second, antimetastatic effects of DDAVP have been demonstrated in the experimental animal models by Dr Alonso's group (6).…”

Cirrhosis, von Willebrand Factor (vWF) and the Low Incidence of Metastatic Malignancy in Injured Liver

“…In this regard, an approach could raise the levels of vWF by a pharmacological intervention. We previously reported that intravenous administration of desmopressin (dDAVP), a synthetic peptide analogue of vasopressin, can inhibit the formation of metastasis in the experimental models of breast and colon cancer at clinically relevant doses [5]. The compound induces an abrupt release of vWF from endothelial cells through a specific agonistic action on V2 vasopressin receptors, with resulting haemostatic and antitumor effects.…”

“…The compound induces an abrupt release of vWF from endothelial cells through a specific agonistic action on V2 vasopressin receptors, with resulting haemostatic and antitumor effects. The perioperative and early postoperative period is an attractive window of opportunity to take advantage from this knowledge, aiming to combat the metastatic disease [5]. Since the release of vWF may favour the collapse of incipient metastatic foci, further evaluation of the dDAVP as well as other vasopressin analogues in clinical trials is warranted.…”