Daniel D. Von Hoff

Novel Therapeutic Targets for Drug Development

There are multiple new therapeutic targets in pancreatic cancer against which new therapies can be directed. There are many targets that have not been discussed in this chapter, including farnesyl transferase,59 asparagine synthase, thymidylate synthase, PTEN/MMAC (phosphatase and tension homolog deleted on chromosome ten/mutated in multiple advanced cancers),60 and others. As we continue to examine fresh human tumors taken at the time of operation, with new molecular biology techniques, many more targets will emerge. These new targets will challenge our drug development efforts as well as our clinical trial designs.

Experimental Therapy: In Vitro Models

Cytotoxic agents have a key role in the treatment of cancer. Unfortunately, the effectiveness of these agents is limited, and their effect on an individual patient’s tumor is frequently difficult to predict. In an effort to improve the therapeutic results of cytotoxic chemical therapy, attempts have been made to develop an in vitro system to predict drug sensitivity in man, much as bacterial culture and sensitivity techniques are used to tailor antibiotic use. Such a system would allow (1) the rapid screening of potential antineoplastic agents, which would aid in the development of promising clinical trials; and (2) the selection of an appropriate chemotherapeutic agent or agents for an individual patient’s tumor.

The Human Tumor Cloning Assay: An In Vitro Assay for Antitumor Activity in Solid Tumors

It is desirable to develop an in vitro system to predict the activity of antineoplastic agents in man, much as bacterial culture and sensitivity techniques are used in the treatment of infectious disease. Such a test would allow the rapid screening of potential anticancer agents for activity and might allow the selection of appropriate chemotherapy for an individual patient’s tumor.