Methylselenocysteine – a promising antiangiogenic agent for overcoming drug delivery barriers in solid malignancies for therapeutic synergy with anticancer drugs

Abstract

Introduction: Despite progress, chemotherapeutic response in solid malignancies has remained limited. Although initial results of the use of antiangiogenic agents in combination chemotherapy indicated an enhanced therapeutic response, recent data indicate that the surviving cancer is not only able to surmount therapy, but also actually able to adapt a more aggressive metastatic phenotype. Thus, selecting an antiangiogenic agent that is less likely to lead to tumor resurgence is a key to future therapeutic success of antiangiogenic agents in a combinatorial setting.

Areas covered: Against the broad spectrum of antiangiogenic agents used at present in the clinic, the putative benefits of the use of organoselenium compounds, such as methylselenocysteine (MSC), are discussed in this review.

Expert opinion: MSC, being part of the mammalian physiology, is a well-tolerated, versatile and economical antiangiogenic agent. It downregulates multiple key upstream tumor survival markers, and enhances tumor drug delivery, at a given systemic dose of an anticancer agent, while protecting normal tissue from cytotoxic adverse effects. Further clinical trials, especially in poorly differentiated cancers, are warranted.

Keywords::

• antiangiogenic therapy
• interstitial fluid pressure
• intratumoral drug delivery
• methylselenocysteine
• selenomethionine
• tumor vascular normalization

Acknowledgements

The author acknowledges the work of his mentor Dr Youcef M Rustum and his group [3,4,8,10,12,16,21,103], which has provided the main impetus for the insights presented in this article.

Notes

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