ABSTRACT
The refinement of combination chemotherapy over the past two decades has significantly increased the median survival time of patients with small cell lung cancer (SCLC) (1 ). However, acquired resistance to multiple drugs is a major obstacle to successful treatment, and despite improvements in survival, chemotherapy is responsible for the cure of less than 10% of patients. Drug resistance in the clinical setting encompasses a broad range of chemotherapeutic agents including alkylating agents, antimetabolites, platinum-containing drugs, hormones, and natural products. In experimental systems, multidrug resistance refers to a phenotype in which tumor cells exposed to a single agent acquire resistance to that agent and become cross-resistant to an extensive group of natural products and their semisynthetic congeners. However, the spectrum of drugs involved in experimental multidrug resistance is narrower than in clinical drug resistance. Nevertheless, the experimental phenotype is relevant in that it includes many clinically useful drugs such as VP-16 (etoposide), doxorubicin, mitoxantrone, and amsacrine (mAMSA).
