Sandra D Castillo1, Eulalia Baselga2, Mariona Graupera1,3. 1. Vascular Signalling Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL). 2. Hospital de la Santa Creu i Sant Pau, Barcelona. 3. CIBERONC, Instituto de Salud Carlos III, Madrid, Spain.
Abstract
PURPOSE OF REVIEW: Recently, it has been discovered that a subset of vascular malformations, of the lymphatic and venous type, are caused by oncogenic mutations in the PIK3CA gene. Now, efforts have been focused in the understanding of the molecular and cellular consequences of these mutations and the opportunities for novel-targeted therapies for these diseases. RECENT FINDINGS: Here, we review the latest findings in the biology of oncogenic PIK3CA mutations in the pathogenesis of vascular malformations. We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformations with special interest in preclinical models for drug testing. Also, we review the latest advances in phosphoinositide 3-kinase (PI3K) inhibitors in the clinic and their repurposing for the treatment of lymphatic malformations and venous malformations. SUMMARY: Oncogenic mutations on PIK3CA causing lymphatic malformations and venous malformations are also frequently found in epithelial cancer. Thus, fundamental research done in the cancer field during the past decades might be applied to the understanding of lymphatic malformations and venous malformations. Likewise, repurposing PI3K pathway inhibitors that are currently in cancer clinical trials can be used as a novel strategy for the treatment of these diseases. Here, we also open a debate for the consideration of lymphatic malformations and venous malformations as developmental tumours.
PURPOSE OF REVIEW: Recently, it has been discovered that a subset of vascular malformations, of the lymphatic and venous type, are caused by oncogenic mutations in the PIK3CA gene. Now, efforts have been focused in the understanding of the molecular and cellular consequences of these mutations and the opportunities for novel-targeted therapies for these diseases. RECENT FINDINGS: Here, we review the latest findings in the biology of oncogenic PIK3CA mutations in the pathogenesis of vascular malformations. We focus on the recent development of in-vitro and in-vivo tools for the study of PIK3CA-mutant vascular malformations with special interest in preclinical models for drug testing. Also, we review the latest advances in phosphoinositide 3-kinase (PI3K) inhibitors in the clinic and their repurposing for the treatment of lymphatic malformations and venous malformations. SUMMARY: Oncogenic mutations on PIK3CA causing lymphatic malformations and venous malformations are also frequently found in epithelial cancer. Thus, fundamental research done in the cancer field during the past decades might be applied to the understanding of lymphatic malformations and venous malformations. Likewise, repurposing PI3K pathway inhibitors that are currently in cancer clinical trials can be used as a novel strategy for the treatment of these diseases. Here, we also open a debate for the consideration of lymphatic malformations and venous malformations as developmental tumours.
Authors: Piotr Kobialka; Helena Sabata; Sandra D Castillo; Mariona Graupera; Odena Vilalta; Leonor Gouveia; Ana Angulo-Urarte; Laia Muixí; Jasmina Zanoncello; Oscar Muñoz-Aznar; Nagore G Olaciregui; Lucia Fanlo; Anna Esteve-Codina; Cinzia Lavarino; Biola M Javierre; Veronica Celis; Carlota Rovira; Susana López-Fernández; Eulàlia Baselga; Jaume Mora Journal: EMBO Mol Med Date: 2022-06-13 Impact factor: 14.260
Authors: Daniel A Snellings; Courtney C Hong; Aileen A Ren; Miguel A Lopez-Ramirez; Romuald Girard; Abhinav Srinath; Douglas A Marchuk; Mark H Ginsberg; Issam A Awad; Mark L Kahn Journal: Circ Res Date: 2021-06-24 Impact factor: 23.213