Biomarker analysis from a pathologist's view. Founding the rationale for personalised treatment of lung cancer

The advent of genomic medicine and sequencing analysis of entire cancer genomes has rapidly improved our understanding of cancer genomics and has defined pathogenetic lesions initiating and driving cancer phenotypes in a causative manner. Moreover rapid development of small molecule inhibitors and highly selective biologicals provided effective tools to intervene with oncogenic signalling resulting from such lesions in the cancer genome. Thereby, the pathologist is now in the position to diagnose causative lesions in the cancer genome as molecular biomarkers directing the selection of patients for effective and highly selective therapies. If oncogenic driver lesions are vigorously validated preclinically and a useful diagnostic test is available, it is possible to provide a proof-of-concept at a very early stage of clinical drug development with the possibility of immediate personal benefit for participants in such phase I/II studies. This approach has significantly changed clinical testing and avoids testing proof for efficacy in large stage III clinical trials at a high failure rate. Therefore, our review summarises recent and paradigmatic progress in lung cancer biomarker diagnostics and defines academic and regulatory requirements for biomarker analysis and selective personalised therapies.