Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. The treatment of
colonic cancer remains difficult because of the lack of effective chemotherapeutic agents; therefore it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs resulting in the inhibition of the development and progression of
cancer. The current knowledge of the modification of
proteins by myristoylation involving
myristoyl-CoA:protein N-myristoyltransferase (NMT) is in its infancy. This process is involved in the pathogenesis of
cancer. We have reported for the first time in rats treated with
azoxymethane that NMT activity was higher in colonic
epithelial neoplasms than in normal colonic tissue and that an increase in NMT activity appeared at an early stage in colonic
carcinogenesis. Increased NMT activity was also confirmed in human colonic
tumors compared to normal tissue. Furthermore,
colorectal tumors displayed increased immunohistochemical staining for NMT compared to normal mucosa in the cytoplasm. In addition, gallbladder
carcinoma showed moderate to strong cytoplasmic positivity for NMT with increased intensity in the invasive component whereas the normal gallbladder mucosa showed weak to negative cytoplasmic staining for this
enzyme. It is conceivable therefore that NMT can be used as a potential marker for the early detection of
cancer. Of particular note is the very recent discovery of cytotoxic compounds in the laboratories of the authors which inhibit NMT and may offer a novel approach for the evolution of candidate
antineoplastic agents which display greater potencies towards
neoplasms than the corresponding normal tissues.