Clinical validation of a revolutionary multi-analyte companion diagnostic platform technology and treatment algorithm for precision medicine

急性髓性白血病（AML）是一种侵袭性血癌，只有约20%的患者在确诊后预计能存活5年或更长时间。一种名为midoschin的新药可以使一些患者的生存时间延长三倍，现在已经可以在NHS上使用。然而，只有一小部分AML患者（约30%）有资格接受这种治疗，其中约50%的患者没有获益；因此，总体而言，只有约15%的AML患者真正受益于治疗。因此，许多患者暴露在不必要的副作用中，被剥夺了参加可能有效的药物试验的机会，NHS在治疗未能受益的患者时遭受了不必要的成本（每年2300万英镑）。用于确定患者是否有资格接受midoin的诊断测试被称为LeukoStrat(r)，该测试评估AML患者的癌细胞是否在FLT3\基因中发生突变。这种“生物标志物”呈阳性的患者将接受midoin治疗。早期临床试验和Kinomica创始人最近的一项临床前研究表明，42-65%没有FLT3突变生物标志物的患者（占所有AML患者的70%）对midoin反应良好，因此可能有大量目前归类为不合格的患者可以从治疗中获益。midoin目前正处于临床试验的晚期阶段，用于无FLT3突变生物标志物的患者。因此，识别那些将从治疗中受益的人变得更加重要，因为NHS治疗无法受益的患者的成本可能会增加两倍。midoin治疗AML（伴有或不伴有FLT3突变）的不同应答率表明，目前FLT3突变生物标志物和检测该标志物的医学检测（LeukoStrat(r)）严重受限。Kinomica的创始人已经开发出一种新的、更准确的方法来预测AML患者是否对midoin有反应。Kinomica的方法包括测量患者癌细胞中一组重要的蛋白质激酶的活性。这个读数可以更好地预测midoin是否会破坏这些细胞。正在寻求资金，以便Kinomica能够将该技术发展为临床试验。认识到激酶活性比基因改变更能预测治疗反应，可能会对许多癌症类型的个性化治疗的发展产生更广泛的影响。”

"Acute myeloid leukaemia (AML) is an aggressive form of blood cancer, where only about 20% of patients are expected to survive for 5 or more years after diagnosis. A new drug called midostaurin can triple survival times for some patients and is now available on the NHS. However, only a subgroup of AML patients (~30%) are eligible to receive this treatment and approximately 50% of those will experience no benefit; therefore, only about 15% of AML patients overall actually benefit from treatment. Consequently, many patients are exposed to unnecessary side-effects, are denied the opportunity to be recruited on trials for drugs that may be effective, and the NHS are subjected to unnecessary costs (\>£23M/year) treating patients that fail to benefit.The diagnostic test used to determine patient eligibility to receive midostaurin is called LeukoStrat(r), which assesses whether an AML patient's cancer cells have mutations in a gene called FLT3\. Patients who are positive for this ""biomarker"" will receive midostaurin.Early clinical trials and a recent pre-clinical study by Kinomica's Founders showed that 42-65% of patients _without_ the FLT3 mutation biomarker (representing 70% of all AML patients) responded well to midostaurin, so there is likely a significant number of patients currently classified as ineligible who could benefit from treatment. Midostaurin is currently in the very advanced stages of clinical trials for use in patients without the FLT3 mutation biomarker. Thus the importance of identifying those who will benefit from treatment becomes even greater, as the cost to the NHS to treat patients who will not benefit could triple.The variable response rates for midostaurin treatment in AML (with and without mutated FLT3), suggest that the current FLT3 mutation biomarker and medical test to detect this marker (LeukoStrat(r)) are severely limited. Kinomica's Founders have developed a new and much more accurate way to predict whether an AML patient will respond to midostaurin. Kinomica's approach involves measuring the activity of an important group of proteins called kinases, within a patient's cancer cells. This readout can then better predict whether midostaurin will destroy those cells. Funding is sought so that Kinomica can develop the technology into a clinical test. The realisation that kinase activities are better predictors of therapeutic response than genetic alterations will likely have far wider implications for the development of personalised therapies across many cancer types."