However, it cited only selected negative studies [1]

However, it cited only selected negative studies [1]. poster child for the precision medicine paradigm. With the discovery of imatinib as a targeted therapeutic for the gene product and its administration to newly diagnosed patients, median survival increased from about five to over 20 years. Other examples of precision medicine\based transformative advances in lethal, previously mostly untreatable cancers include imatinib as a c\KIT inhibitor in gastrointestinal stromal tumors, crizotinib in inhibitors in lung cancer, BRAF/MEK inhibitors in melanoma, HER2/neu\targeted therapies in breast cancer, anti\CD30 antibody drug conjugates in Hodgkin disease and anaplastic lymphoma, sonic hedgehog inhibitors in basal cell cancer, and RET inhibitors in medullary thyroid cancer. Most or all of these advances were defined on the basis of randomized clinical SYP-5 trials Despite these advances, a recent perspective article in a major journal argued that precision medicine is an illusion. However, it cited only selected negative studies [1]. The importance of genomic testing and matching patients to the right drug is readily apparent from each of the above breakthroughs [2]. In that perspective, the studies cited did indeed show minimal if any improvement in the primary outcomes. In light of the wealth of positive studies, a critical analysis of the negative trials is required. As an example, the negative SHIVA randomized trial is often mentioned as an example to bolster the argument that precision medicine is a failure [3]. SHIVA is important, as it demonstrated that a randomized precision medicine trial could be conducted. However, approximately 80% of the patients in SHIVA were matched to single\agent mTOR or hormone modulators. Hence, it ARNT is reasonable to conclude that matched monotherapy with these agents in the advanced cancer setting is not effective. The corollary that all precision medicine is a failure extrapolates the finite observations in this trial to settings that were not adequately explored in the SHIVA trial and is, hence, not justifiable. The article also quotes an MD Anderson study that showed that only 6.4% of patients who were sequenced could be SYP-5 paired with an agent [4]. However, more recent data from the same institution and others demonstrate that about 25% of patients tested could be matched to a drug [5], [6], with the higher percentages in the latter studies at least partially due to the greater yield of potentially actionable alterations with the use of larger, more robust next\generation sequencing gene panels. Other factors that limit the utility of genomic testing need to be acknowledged, most prominently the fact that profiling is often applied to heavily pretreated, end\stage patients [5], [6], [7]. Finally, despite these limitations, three meta\analyses totaling approximately 85,000 patients demonstrated that the precision paradigm, that is, biomarker\driven matching, was safe and independently associated with improvement in all outcome SYP-5 variables [8], [9], [10]. Furthermore, the response rate was a remarkable 42% in phase I studies that used a genomic biomarker. Additionally, these meta\analyses demonstrated the futility of not using precision medicine, that is, of targeted therapeutics applied without a biomarker. In the latter types of studies, median response rates were only about 5% across trials, and outcome parameters were significantly worse than with any other type of study, including those of trials with traditional cytotoxics. Another major emerging element that must be considered in the context of precision therapy is immunology\based treatment and its marriage SYP-5 with genomics. It is becoming clear that the immune system recognizes the mutanome. Furthermore, molecular anomalies such as amplification in Hodgkin disease, mismatch repair gene defects in colorectal cancer, and high tumor mutational burden serve as biomarkers that predict striking and durable response rates. The opponent of precision medicine [1] also commented.