Ever since the International Human GenomeSequencing Consortium unveiled its “working draft” of the human genome sequence in 2000, the scientific community has eagerly discussed and speculated on the potential of genomic medicine. Patients, clinicians, and scientists were—and still are—excited about the possibilities of targeted therapies such as imatinib (Gleevec) for chronic myeloid leukemias and gastrointestinal stromal tumors and trastuzumab (Herceptin) for HER2/neu-positive breast cancer. There has been significant progress in the development of these and other targeted therapies, and they remain part of an intriguing and promising work in progress. However, for patients with lung cancer and melanoma, both of which are highly refractory diseases, the therapeutic choices other than chemotherapy have been limited and the commensurate outcomes discouraging.
In the early 2000s, we were excited about targeted therapies such as gefitinib (Iressa), which blocks epidermal growth factor receptor (EGFR)- tyrosine kinase activity in non-small cell lung cancer (NSCLC), but its clinical benefit was still limited. We have since gained a better understanding of lung cancer as a molecularly heterogeneous disease and have adjusted our approach to its treatment, based on new data showing that all lung cancer patients cannot be treated with the same drug regimen and achieve the same outcomes. With those insights, the implications of targeted therapies came into sharper focus in 2004 with the US Food and Drug Administration (FDA) approval of erlotinib (Tarceva) for the 10%–15% of patients with NSCLC (adenocarcinoma) who have the EGFR gene mutation. At around the same time, scientists identified BRAF gene mutations in about 40%– 60% of patients with melanoma, and the quest for therapies for that disease was redirected to the cellular level as well. ...
* For a PDF of the full article, click in the link to the left of this introduction.