高通量方法调查肿瘤组学格局，已迅速将肿瘤专家推进精准医学的时代。精准医学的重要教训之一可能是，为精准，治疗必须个性化，因为每种癌症的复杂分子和免疫格局都有所不同。转化性疗法包括针对分子异常的后遗症或免疫机制的疗法，并且越来越多之前被认为难以应药的途径已成为可应药的途径。应用精准医学的关键是选择每个患者的正确药物组合，并在疾病的正确阶段使用。令人棘手的治疗选择问题还包括证据表明有害突变在正常组织和非恶性状况中很常见。宿主的角色在确定治疗反应方面也很关键，特别是对于免疫疗法而言更是如此。实际上，最大程度地提高免疫疗法的影响将需要组学分析，将正确的免疫靶向药物与个体化的患者和肿瘤设置相匹配。在本文中，我们讨论了六个关键谜题，这是优化精准医学应用于致命肿瘤的必经之路。© 2022. Springer Nature Limited.

High-throughput methods to investigate tumour omic landscapes have quickly catapulted cancer specialists into the precision oncology era. The singular lesson of precision oncology might be that, for it to be precise, treatment must be personalized, as each cancer's complex molecular and immune landscape differs from patient to patient. Transformative therapies include those that are targeted at the sequelae of molecular abnormalities or at immune mechanisms, and, increasingly, pathways previously thought to be undruggable have become druggable. Critical to applying precision medicine is the concept that the right combination of drugs must be chosen for each patient and used at the right stage of the disease. Multiple puzzles remain that complicate therapy choice, including evidence that deleterious mutations are common in normal tissues and non-malignant conditions. The host's role is also likely to be key in determining treatment response, especially for immunotherapy. Indeed, maximizing the impact of immunotherapy will require omic analyses to match the right immune-targeted drugs to the individualized patient and tumour setting. In this Perspective, we discuss six key riddles that must be solved to optimize the application of precision oncology to otherwise lethal malignancies.© 2022. Springer Nature Limited.