PIK3CA is one of the most commonly mutated genes in solid cancers. PIK3CA mutations are also found in benign overgrowth syndromes, collectively known as PIK3CA-related overgrowth spectrum (PROS). As in cancer, PIK3CA mutations in PROS arise postzygotically, but unlike in cancer, these mutations arise during embryonic development, with their timing and location critically influencing the resulting disease phenotype. Recent evidence indicates that phosphoinositide 3-kinase (PI3K) pathway inhibitors undergoing trials in cancer can provide a therapy for PROS. Conversely, PROS highlights gaps in our understanding of PI3K’s role during embryogenesis and in cancer development. Here, we summarize current knowledge of PROS, evaluate challenges and strategies for disease modeling, and consider the implications of PROS as a paradigm for understanding activating PIK3CA mutations in human development and cancer.

PIK3CA是实体癌中最常见的突变基因之一。 PIK3CA突变也见于良性过度生长综合征，统称为PIK3CA相关过度生长谱 (PROS)。与癌症一样，PROS 中的PIK3CA突变在合子后出现，但与癌症不同的是，这些突变在胚胎发育过程中出现，其发生的时间和位置严重影响最终的疾病表型。最近的证据表明，正在进行癌症试验的磷酸肌醇 3 激酶 (PI3K) 通路抑制剂可以为 PROS 提供治疗方法。相反，PROS 凸显了我们对 PI3K 在胚胎发生和癌症发展过程中的作用的理解上的差距。在这里，我们总结了 PROS 的当前知识，评估了疾病建模的挑战和策略，并考虑了 PROS 作为理解人类发育和癌症中激活PIK3CA突变的范例的影响。