Cancer-associated PIK3CA mutations in overgrowth disorders

TY - JOUR

T1 - Cancer-associated PIK3CA mutations in overgrowth disorders

AU - Madsen, Ralitsa R.

AU - Vanhaesebroeck, Bart

AU - Semple, Robert K.

N1 - Funding Information: We thank Rachel Knox for help assembling Figure 2 . R.K.S. and R.R.M. are supported by the Wellcome Trust (grants 210752/Z/18/Z and 105371/Z/14/Z , respectively) and by the UK NIHR Cambridge Biomedical Research Centre . B.V. is supported by Cancer Research UK ( C23338/A15965 ), PTEN Research and the UK NIHR University College London Hospitals Biomedical Research Centre . Publisher Copyright: © 2018 The Authors

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

KW - cancer

KW - overgrowth syndromes

KW - PI3K

KW - PIK3CA

UR - https://www.scopus.com/pages/publications/85052976289

U2 - 10.1016/j.molmed.2018.08.003

DO - 10.1016/j.molmed.2018.08.003

M3 - Review article

C2 - 30197175

AN - SCOPUS:85052976289

SN - 1471-4914

VL - 24

SP - 856

EP - 870

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 10

ER -