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Personalised Treatment Editorial Molecular Profiling – Challenges and Perspectives Christian Dittrich Professor of Medicine, Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna) – LB Cluster Translational Oncology; Applied Cancer Research – Institution for Translational Research (ACR-ITR VIEnna), Kaiser Franz Josef-Spital, Vienna, Austria Abstract Molecular profiling is today’s answer to the eternal unmet need of personalising anticancer therapy. We have never reached such a level of rationality before, based on new technologies, knowledge of systems biology and insights into patho-mechanisms. Whereas we actually focus mainly on mutations of a limited number of cancer genes, we will also have to integrate epigenetic, transcriptional and post-transcriptional changes into our future therapeutic considerations. Overall, we have reached an advanced level of stratified medicine, but are still on the way of targeting the holy grail of real personalisation. Keywords Molecular profiling, precision medicine, personalised medicine, stratified medicine Disclosure: Christian Dittrich has no conflicts of interest to declare. No funding was received in the publication of this article. Received: 19 November 2014 Accepted: 2 December 2014 Citation: European Oncology & Haematology, 2014;10(2):102–3 Correspondence: Christian Dittrich, Director of LB-Institute for Applied Cancer Research and Head of Centre for Oncology and Haematology, Kaiser Franz Josef-Spital, Kundratstrasse 3, 1100 Vienna, Austria. E: Molecular profiling is becoming undoubtedly more and more part of the workup of cancer patients. The fact that tumour profiling is not restricted anymore, to be used within the scientific frame to upgrade the level of stratification in clinical trials or to test whether the integration of this methodology, will even allow individualisation of cancer treatment, which makes it necessary to critically define its actual position. Such an attempt of positioning whether, based on its overall scientific accuracy and reliability, its use is justified in the clinical routine is eagerly warranted since it has already been commercially propagated and advertised. Personalising cancer medicine is a logical path that has been pursued by generations of oncologists. It is based on the trivial finding that individual human beings behave differently in terms of the same pharmacotherapeutic intervention against their similar tumours with regard to histology. Various methodologies have been developed to individualise anticancer therapy, but none of them, neither the clonogenic assay as published by Von Hoff et al. 1 nor the adenosine-triphosphate (ATP)-based chemosensitivity assay (TCA) used by Cree et al., 2 have been proved to generate superior treatment results in comparison to treatment choice based on the respective best available standard. With molecular profiling, a level of precision medicine has been touched upon that had never been reached before. Nevertheless, the same principal questions have to be asked and confirmed before we are justified to propagate it as the oncologic panacea of the 21st century. In a first attempt in this direction, Cobo et al., 3 who compared standard treatment with biomarker-based selected chemotherapy in non-small 102 cell lung cancer, only found an advantage for objective response, but not for progression-free and overall survival (PFS/OS). Large screening programmes have been set up at renowned institutions worldwide to offer patients clinical trials evaluating drugs that matched specific identified molecular alterations determined with different technologies. Retrospective analyses of such trial programmes turned out to provide generally results of improved outcome compared with historical controls. 4–6 There are different types of ongoing trials using molecular profiling prospectively. According to Le Tourneau et al. 7 they can be subdivided into stratified and algorithm-based ones. The stratified trials are mainly used to test the efficacy of drugs. The patient allocation to the different targeted drugs may be started at random or an adaptive design based on the respective molecular profile may be used upfront. This series of trials have started with the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) initiative at the MD Anderson Cancer Centre in the field of advanced pre-treated non- small cell lung cancer and have spread since then with the FOCUS 4 trial to remission maintenance after first-line treatment of colorectal cancer and have embarked on the preoperative, neo-adjuvant setting with the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2 (I-SPY 2) trial in breast cancer. The latter yielded the early assessment of activity of the PARP inhibitor veliparib and of the irreversible HER-2 inhibitor neratinib. By contrast, histology-stratified or so-called basket trials evaluate a targeted drug in various tumour entities with presence of the respective molecular target. Among them, the basket study testing vemurafenib (VE-BASKET) and the CREATE trial testing crizotinib in various tumours © Touc h ME d ic al ME d ia 2014