A possible role for cyclosporins in cancer chemotherapy.

It has been established for some time that cyclosporin A (CsA) can exert cytotoxic effects in T-cell neoplasms. More recently, antiproliferative effects in a variety of non-T-cell tumour cell lines have been demonstrated. Inhibition of polyamine synthesis is a possible mechanism and combination of CsA with other polyamine inhibitors may be particularly effective. The non-immunosuppressive analogue, B3-243, is at least as effective as CsA as an antiproliferative in human lung cancer cell lines. CsA potentiates the effect of a number of cytotoxic drugs (eg adriamycin, vincristine, VP16) both in vitro and in vivo. Differential potentiation in vitro is often seen in cells with acquired drug resistance compared with their parent lines. A number of non-immunosuppressive analogues of CsA also act as 'resistance modifiers' and hence the structure/activity requirements for immunosuppression and resistance modification appear to differ.