Novel Chemotherapeutic Agents

NOVEL CHEMOTHERAPEUTIC AGENTS

The next horizon for cancer treatment is molecularly tar-geted agents, cancer vaccines, and gene therapy. Several drugs are currently available that target specific mole-cules or proteins in cancer cells. For example, trastuzumab is a DNA-derived monoclonal antibody to the human epidermal growth factor receptor 2 protein (HER-2). Treatment with trastuzumab is currently indicated in patients with metastatic breast cancer whose tumors over-express HER-2. Some ovarian, cervical, and endometrial tumors express the HER-2/neu receptor; therefore, investi-gation is currently ongoing regarding the usefulness of this agent in gynecologic tumors. Additionally, bevacizumab is a monoclonal antibody designed to target the VEGF pro-tein and inhibit angiogenesis in tumors. It is currently under investigation for possible treatment of a variety of tumors, including epithelial ovarian cancer.

Tumor vaccines are also currently being investigatedfor the treatment of ovarian cancer. The underlying princi-ple behind these therapeutic vaccines is to inoculate the patient with a modified cancer cell line in an attempt to stimulate the patient’s immune system to recognize and eliminate the tumor. Inactivated virus strains have also been studied as a vector for the vaccines in hopes of creating higher immunogenicity. Currently the response to this type of therapy has been modest, but studies are ongoing.

Because a large proportion of gynecologic cancers result from loss of genetic function through DNA muta-tions, investigational therapies have also focused on genetic manipulation of the tumors, or gene therapy. For instance, because half of ovarian cancers exhibit deleterious muta-tions in the p53 gene, research has focused on delivering a normal p53 gene product to the tumor using a variety of viral vectors. The hope is that the wild-type gene product would then be expressed by the tumor and the growth would then be inhibited. So far, response has been minimal, but investigation continues.

The potential benefits of these novel therapeutic con-cepts are manifold, whether considered as primary or adjunct therapy. Work in this area is in the experimental stage,but the goal of eliminating cancer cells with minimal toxicity remains the goal of cancer therapeutics.