Elizabeth M. Jaffee, MD

The identification of key signaltransduction pathways and, inparticular, specific proteins thatare involved in the regulation of cancercell growth has provided unprecedentedopportunities for researchersinterested in targeted cancer treatment.The identification of molecular target-specific therapy offers the potentialof maximal therapeutic benefitwhile minimizing toxicity to normalcells. The accomplishment that led tothe sequencing and analysis of theentire human genome in 2001 has providedresearchers with the basic criticaltools to begin to identify anddifferentiate cancer from normal tissueat the genetic level.[1,2] Whilethe implications of this landmarkachievement are still being realized,it has become evident that the identificationof critical genes and proteinsinvolved in cell division and growthare just the beginning. The complexrelationships between multiple signaltransduction pathways, the surroundingtumor microenvironment, andpathways involved in immune-systemregulation have gained new appreciation.The ability to manipulate thesemultiple interactive systems with targetedtherapies represents a new treatmentparadigm in oncology.

Advances in biotechnology and basic immunology have convergedto create an unprecedented opportunity to use vaccines to harness thepower of the immune system in the fight against breast cancer. Cancervaccines have several therapeutic advantages over more traditionalbreast cancer treatment modalities. First, targeting the antitumorimmune response to critical tumor-specific antigens defines a therapywith exquisite specificity and minimal toxicity. Second, immune-mediatedtumor destruction occurs by mechanisms distinct from those underlyingthe efficacy of chemotherapy and hormone therapy. Thus, immunotherapyoffers an approach to circumventing the intrinsic drugresistance that currently underlies therapeutic failure. Third, thephenomenon of immunologic memory endows immunotherapy withthe potential for creating a durable therapeutic effect that is reactivatedat the onset of disease relapse. Moreover, immunologic memory alsounderlies the potential future use of vaccines for the prevention ofbreast cancer. Early clinical trials have highlighted the promise ofbreast cancer vaccines, and have further defined the challenges facingtranslational scientists and clinical investigators. The judicious applicationof laboratory advances to clinical trial design should facilitatethe development of immunotherapy as an additional major therapeuticmodality for breast cancer, with the potential for breast cancer preventionas well as treatment.

Although surgery remains the only curative option for patients with gastrointestinal (GI) malignancies, the use of adjuvant chemotherapy and/or localized radiation is considered standard therapy for patients who present with