title: The use of peptide analogs for the treatment of gastrointestinal, pancreatic, liver and urinary bladder cancers.
abstract: Peptide hormones can influence the development and growth of many cancers which are not considered classical hormone-dependent tumors. Analogs of somatostatin, bombesin/gastrin-releasing peptide (GRP), luteinizing hormone-releasing hormone (LH-RH) and growth hormone-releasing hormone (GH-RH) can interfere with receptors on tumor cells or intracellular pathways that are important in cell proliferation and in this way inhibit tumor growth. The first part of this review explains how these peptide hormones and their analogs affect tumors. The second part of this review describes how various hormone analogs can be used for the treatment of gastric, colorectal, pancreatic, liver and urinary bladder cancers. These tumors are major health problems worldwide and their treatment remains a great challenge. Receptors for somatostatin, bombesin/GRP, LH-RH and GH-RH are present in a large percentage of these cancers. We have developed a series of cytotoxic peptides based on doxorubicin or its derivative 2-pyrrolino-doxorubicin coupled to an analog of LH-RH, somatostatin or bombesin. This new class of targeted analogs might provide a more effective therapy for various cancers that express receptors for these carrier peptides, while producing significantly reduced peripheral toxicity. Under experimental conditions, these peptide hormone analogs strongly inhibited the growth of these tumors. Cytotoxic analogs were particularly effective on tumors that express the specific peptide receptors and acted more powerfully than the carrier peptide or the cytotoxic compound alone. Clinical trials on these peptide analogs are in progress.
authors.forename: Karoly
authors.initials: K
authors.lastname: Szepeshazi
authors.forename: Norman L
authors.initials: NL
authors.lastname: Block
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally