PIK3CA相关疾病包括许多罕见和超罕见的疾病,由过度激活PI3K-AKT-mTOR信号通路的体细胞遗传变异引起,这对细胞周期控制至关重要。PIK3CA相关疾病包括PIK3CA相关的过度生长谱(PROS),PIK3CA相关血管畸形和PIK3CA相关非血管病变。表型是极其异质和重叠的。因此,诊断和管理经常涉及各种健康专家。鉴于这些疾病的罕见性和提供最佳护理的中心数量有限,意大利Macrodactyly和PROS协会科学委员会提出了对最新诊断建议的修订,分子检测,临床管理,后续行动,和治疗策略。这些建议提供了对分子诊断的见解,合格样品,优选的测序,以及阴性结果的验证方法和管理。本文的目的是通过共同的共享方法促进医疗保健中心和临床医生之间的合作。最后,我们提出了当前和未来研究的方向,包括新的全身靶向治疗,目前正在几项临床试验中进行评估,例如可用于下调信号通路的特异性抑制剂。
PIK3CA-related disorders encompass many rare and ultra-rare conditions caused by somatic genetic variants that hyperactivate the PI3K-AKT-mTOR signaling pathway, which is essential for cell cycle control.
PIK3CA-related disorders include
PIK3CA-related overgrowth spectrum (PROS),
PIK3CA-related vascular malformations and
PIK3CA-related non-vascular lesions. Phenotypes are extremely heterogeneous and overlapping. Therefore, diagnosis and management frequently involve various health specialists. Given the rarity of these disorders and the limited number of centers offering optimal care, the Scientific Committee of the Italian Macrodactyly and PROS Association has proposed a revision of the most recent recommendations for the diagnosis, molecular testing, clinical management, follow-up, and treatment strategies. These recommendations give insight on molecular diagnosis, eligible samples, preferable sequencing, and validation methods and management of negative results. The purpose of this paper is to promote collaboration between health care centers and clinicians with a joint shared approach. Finally, we suggest the direction of present and future research studies, including new systemic target therapies, which are currently under evaluation in several clinical trials, such as specific inhibitors that can be employed to downregulate the signaling pathway.