Introduction

Drug resistance is the single most important stumbling block in the fight against metastatic cancer. In fact, 90% of the advanced cancers that can be eradicated by chemotherapy are rare tumor types, which altogether account for only 10% of all malignant tumor types. Tumor types that are responsive for chemotherapy can be categorized into three groups, according to whether chemotherapy produces cure, survival gain, or no survival gain (see also Table 6.1):

1. Tumor types in which a large fraction of patients can be cured. Here we should differentiate between those patients with advanced disease and those treated in an adjuvant setting for microscopic disease. Classical examples of the former include female choriocarcinoma, testicular carcinoma, and Hodgkin's disease. The best examples of microscopic disease that is curable with adjuvant chemotherapy are childhood embryonal rhabdomyosarcoma and breast and colon cancer in adults.

2. Advanced cancers that respond to systemic therapy resulting in an overall survival benefit. The best example of this category is advanced breast cancer.

3. Cancer types in which a small fraction of patients respond but an overall survival benefit is not achieved. Most representative of this category is colorectal cancer, where only responding patients show a survival benefit. This effect in responders is not translated into an overall survival advantage.

Nearly 50% of all patients with cancer suffer from malignancies that are intrinsically resistant to chemotherapy.