Recent evidence suggests that the biology of noncutaneous melanoma differs significantly from cutaneous melanoma and may provide therapeutic opportunity. The most frequent sites of origin of noncutaneous melanoma are the eye and mucosal surfaces. Although noncutaneous melanomas are an uncommon group of cancers (representing less than 10% of all melanomas) a greater understanding of their genetic and molecular abnormalites is being translated into novel treatment strategies. These developments are important because there is currently no effective systemic therapy for noncutaneous melanoma. Significant attention has been focused on the role of c-kit (KIT, CD117), a transmembrane receptor with tyrosine kinase activity. In vitro and ex vivo evidence suggests that c-kit is frequently expressed/over expressed/mutated in noncutaneous melanoma. Anti-tumour effects with c-kit inhibitors are seen in pre-clinical models. A variety of multitargeted kinase inhibitors which have activity against c-kit are currently in early phase clinical trials in metastatic ocular, mucosal and acral melanoma. The few case reports of significant clinical activity with targeted therapies provides hope that greater understanding of the biology of noncutaneous melanoma can be translated into effective treatment.
Antibody therapies have become an important component in the management of malignant disease. Recombinant technology offers enormous opportunities to tailor antibodies to meet clinical requirements. This includes the reduction of immunogenicity and the development of smaller antibody fragments that can be incorporated into fusion proteins. Antibodies can block tumour growth factors or their receptors, activate immunological attack on the tumour, or be used to deliver payloads such as radioisotopes, cytotoxic drugs or toxins. Pretargeting includes streptavidin/biotin systems and antibody-directed enzyme prodrug therapy (ADEPT). ADEPT uses an antibody-enzyme complex to deliver a prodrug-activating enzyme to tumours for selective prodrug conversion at the tumour site. New antibody targets, refined antibodies, antibody fusion proteins, combination therapies and the use of antibodies as adjuvant therapy are important topics in the development of antibody therapy against cancer.
Monoclonal antibodies (mAbs) are being explored as an anticancer therapy of growing importance and formidable potential. The exquisite specificity of antibodies provides an ideal mechanism for targeted cancer therapy. Using hybridoma technology, antibody libraries, or transgenic mice, high‐affinity antibodies can be generated against an extensive range of targets. Recombinant technology is enabling the production of fully human mAbs, smaller mAb‐based molecules, and multifunctional fusion proteins. mAbs can target a growth factor or its receptor, initiate an immunological assault, activate apoptosis, or deliver a cytotoxic payload such as a radioisotope. Several antibody‐based therapies are now licensed to treat haematological or solid tumour malignancies. This chapter explores the structure and function of antibodies, the application of recombinant technology to mAbs and the therapeutic effects of mAbs on cancer.
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