Published in Cancer Detection and Prevention 1998; 22(1):62-67.

Epidermal Growth Factor-Related Peptides as Targets for Experimental Therapy of Human Colon Carcinoma

Nicola Normanno MDa, Antonella De Luca PhDa, David S Salomo PhDa,b, Fortunato Ciardiello MDC

aOncologia Sperimentale D, ITN-Fondazione Pascale, Naples, Italy; bTumor Growth Factor Section, LTIB, National Cancer Institute, National Institutes of Health, Bethesda, MD; cCattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Facolta di Medicina e Chirurgia, Universita Federico II, Naples, Italy

Address all correspondence and reprint requests to: Nicola Normanno, M.D., Oncologia Sperirnentale D, ITN-Fondazione Pascale, 80131 Naples, Italy.

ABSTRACT: Colorectal carcinomas generally show a poor sensitivity to conventional chemotherapeutics Therefore, novel therapeutic approaches are required to improve the prognosis of colon cancer patients in advanced stage. Several growth factors are involved in the control of colon carcinoma cell proliferation. In particular, the epidermal growth factor (EGF)-related peptides transforming growth factor-alpha (TGF-alpha) amphiregulin (AR), and CRIPTO (CR) are frequently overexpressed in human colon carcinomas. It has also been recently demonstrated that they can function as autocrine growth factors in human colon carcinoma cells. In fact, antisense (AS) retroviral expression vectors or AS oligonucleotides directed against TGF-alpha, AR, or CR are able to inhibit growth and transformation of several human colon carcinoma cell lines. These data suggest that the EGF like growth factors and their receptors offer potential as targets for experimental therapy of human colon carcinoma. This article reviews the most recent findings in this field.

KEY WORDS: antisense oligonucleotides, colon cancer, growth factors.