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 - http://www.scopus.com/inward/record.url?scp=85052976289&partnerID=8YFLogxK
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 -
