Many clinical approaches for the treatment of
hormone-sensitive
tumors are being developed based on analogs of
LH-RH and
somatostatin. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of
LH-RH agonists like [D-Trp6]-
LH-RH and new
LH-RH antagonists free of edematogenic effects such as [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10]-
LH -RH (SB-75). Agonists and antagonists of
LH-RH have been used in patients with
prostate cancer and might be also beneficial for the treatment of
breast cancer and ovarian, endometrial and
pancreatic carcinomas. Some of the effects of
LH-RH analogs can be due to direct action since
LH-RH receptors have been found in these
cancers. The use of sustained delivery systems based on
microcapsules of PLG, makes the treatment more efficacious. Octapeptide analogs of
somatostatin such as
D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for antitumor activity. These
somatostatin analogs, by virtue of having a wide spectrum of activities appear to inhibit various
tumors through multiple mechanisms. Direct antiproliferative actions of
somatostatin analogs appear to be mediated by specific receptors located on
tumor cells. High affinity binding sites for
RC-160 and related analogs have been found in human pancreatic, prostate, breast and
ovarian cancers and
brain tumors such as
meningiomas. In vivo administration of analog
RC-160 inhibits the growth of Dunning R-3327
prostate cancers in rats, MXT mammary
tumors in mice and BOP-induced ductal
pancreatic cancers in hamsters. Combination of
microcapsules of
RC-160 with [D-Trp6]-
LH-RH results in synergistic potentiation of the inhibition of these
cancers.
Somatostatin analog
RC-160 and
LH-RH antagonist
SB-75 are the object of further experimental studies and clinical trials aimed at the exploration of their inhibitory effects on the processes of malignant growth.