[Therapy for non-small cell lung cancer: new concepts based on molecular biology]

Recent advances in molecular biology have broadened our knowledge of the biological characteristics of cancer. In the present paper, we review and discuss new modalities of therapy for non-small cell lung cancer (NSCLC) based on biological findings. These modalities include: 1) diagnosis of cancer based on gene abnormalities: 2) decision making on chemo-/radiotherapy based on new biological findings: 3) gene therapy: and 4) new chemotherapeutic agents. Mutation of the p53 gene, which occurs most frequently in NSCLC, is a well-documented molecular target in these modalities. The development of polymerase chain reaction technology has enabled early diagnosis of NSCLC by detection of p53 gene abnormalities in sputum. Transfer of the wild-type p53 gene using a retrovirus vector to cancer tissues with mutant p53 gene has already been tested clinically. Inhibition of tumor neovascularization has been studied extensively in attempts to develop noveal chemotherapeutic agents. Angiostatin or endostatin, an inhibitor of tumor neovascularization is in clinical use. Matrix metalloprotease inhibitions (MMPs) also inhibit neovascularization of tumors. Marimastat, an oral MMP, is expected to prevent cancer metastasis.