Hyaluronidase as an Additive in Cancer Chemotherapy
One major limitation of cancer
chemotherapy appears to be the poor penetration of drugs due to
enhanced intratumoural pressure and natural barriers such as the
hyaluronan enriched stroma. As a component of the intercellular matrix
hyaluronic acid seems to be an interesting target for the circumvention
of drug resistance by co-administration of hyaluronidase. Regardless of
the mechanism of action, i.e. either improved availability of the
chemotherapeutics or chemosensitization by disruption of
adhesion-dependent multicellular drug resistance, studies with
experimental mammary carcinomas have shown that hyaluronidase is able
to disrupt intercellular adhesion and to chemosensitize tumor cells by
a mechanism, independent of increased drug penetration (cf. Cancer Letters 131
no.1, (1998), special issue: Role of the tumour microenvironmet in
resistance to cytotoxic drugs). Whatever the mechanism, several
experimental and clinical studies suggest the benefit of combining
hyaluronidase with chemotherapeutics.
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