Stock Julie K, Jones Neil P, Hammonds Tim, Roffey Jon, Dillon Christian
Cancer Research Technology Discovery Laboratories, London, UK.
Cancer Research Technology Discovery Laboratories, London, UK
J Biomol Screen. 2015 Mar;20(3):305-17. doi: 10.1177/1087057114564349. Epub 2015 Jan 22.
Translating existing and emerging knowledge of cancer biology into effective novel therapies remains a great challenge in drug discovery. A firm understanding of the target biology, confidence in the supporting preclinical research, and access to diverse chemical matter is required to lower attrition rates and prosecute targets effectively. Understanding past successes and failures will aid in refining this process to deliver further therapeutic benefit to patients. In this review, we suggest that early oncology drug discovery should focus on selection and prosecution of cancer targets with strong disease biology rather than on more chemically "druggable" targets with only modest disease-linkage. This approach offers higher potential benefit but also increases the need for innovative and alternative approaches. These include using different methods to validate novel targets and identify chemical matter, as well as raising the standards and our interpretation of the scientific literature. The combination of skills required for this emphasizes the need for broader early collaborations between academia and industry.
将癌症生物学的现有知识和新出现的知识转化为有效的新型疗法，仍然是药物研发中的一项巨大挑战。要降低损耗率并有效地推进靶点研究，需要对靶点生物学有深入的理解、对支持性临床前研究有信心，以及能够获取多样化的化学物质。了解过去的成功与失败将有助于完善这一过程，为患者带来更多治疗益处。在本综述中，我们认为早期肿瘤药物研发应侧重于选择和推进具有强大疾病生物学依据的癌症靶点，而非仅仅关注与疾病关联较弱但化学上更具“可成药性”的靶点。这种方法具有更高的潜在益处，但也增加了对创新和替代方法的需求。这些方法包括使用不同的方法来验证新靶点和识别化学物质，以及提高科学文献的标准和我们对其的解读。为此所需的技能组合强调了学术界和产业界在早期进行更广泛合作的必要性。
