. 2019 May;30(7).
doi: 10.1093/annonc/mdz133.

Targeting the PI3-kinase pathway in triple-negative breast cancer

J Pascual 1 N C Turner 2 
  • PMID: 31050709
  •     15 citations


Triple-negative breast cancer (TNBC) is characterised by poor outcomes and a historical lack of targeted therapies. Dysregulation of signalling through the phosphoinositide 3 (PI3)-kinase and AKT signalling pathway is one of the most frequent oncogenic aberrations of TNBC. Although mutations in individual genes occur relatively rarely, combined activating mutations in PIK3CA and AKT1, with inactivating mutations in phosphatase and tensin homologue, occur in ∼25%‒30% of advanced TNBC. Recent randomised trials suggest improved progression-free survival (PFS) with AKT-inhibitors in combination with first-line chemotherapy for patients with TNBC and pathway genetic aberrations. We review the evidence for PI3K pathway activation in TNBC, and clinical trial data for PI3K, AKT and mammalian target of rapamycin inhibitors in TNBC. We discuss uncertainty over defining which cancers have pathway activation and the future overlap between immunotherapy and pathway targeting.

Keywords: AKT; PI3K; PTEN; predictive biomarkers; targeted therapy; triple-negative breast cancer.

Efficacy of PI3K inhibitors in advanced breast cancer.
B Verret, J Cortes, +2 authors, M Arnedos.
Ann Oncol, 2019 Dec 21; 30(Suppl_10). PMID: 31859349    Free PMC article.
Cystatin SN Affects Cell Proliferation by Regulating the ERα/PI3K/AKT/ERα Loopback Pathway in Breast Cancer.
Yanfang Liu, Hong Ma, +2 authors, Jing Yao.
Onco Targets Ther, 2020 Jan 11; 12. PMID: 31920327    Free PMC article.
Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating miRNA-22-3p/akt2 In Vitro And In Vivo.
Xichang Zhou, Xiang Wang, +3 authors, Yangmei Zhang.
Onco Targets Ther, 2019 Dec 06; 12. PMID: 31802908    Free PMC article.
Rosemary Extract Inhibits Proliferation, Survival, Akt, and mTOR Signaling in Triple-Negative Breast Cancer Cells.
Alina Jaglanian, Evangelia Tsiani.
Int J Mol Sci, 2020 Feb 06; 21(3). PMID: 32012648    Free PMC article.
Fertility preservation in breast cancer with case-based examples for guidance.
Mary E Hampe, Alice S Rhoton-Vlasak.
J Assist Reprod Genet, 2020 Feb 03; 37(3). PMID: 32008180    Free PMC article.
High-throughput, Label-Free Quantitative Proteomic Studies of the Anticancer Effects of Electrical Pulses with Turmeric Silver Nanoparticles: an in vitro Model Study.
Lakshya Mittal, Ignacio G Camarillo, +3 authors, Raji Sundararajan.
Sci Rep, 2020 May 01; 10(1). PMID: 32350346    Free PMC article.
Molecular subtypes and precision treatment of triple-negative breast cancer.
Shen Zhao, Wen-Jia Zuo, Zhi-Ming Shao, Yi-Zhou Jiang.
Ann Transl Med, 2020 May 13; 8(7). PMID: 32395543    Free PMC article.
Role of BET Inhibitors in Triple Negative Breast Cancers.
Durga Khandekar, Venkataswarup Tiriveedhi.
Cancers (Basel), 2020 Mar 29; 12(4). PMID: 32218352    Free PMC article.
ADAM17-regulated CX3CL1 expression produced by bone marrow endothelial cells promotes spinal metastasis from hepatocellular carcinoma.
Chi Sun, Annan Hu, +5 authors, Jian Dong.
Int J Oncol, 2020 Apr 23; 57(1). PMID: 32319605    Free PMC article.
Neoadjuvant Treatment for Triple Negative Breast Cancer: Recent Progresses and Challenges.
Jin Sun Lee, Susan E Yost, Yuan Yuan.
Cancers (Basel), 2020 Jun 04; 12(6). PMID: 32486021    Free PMC article.
Biomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives.
Stefania Cocco, Michela Piezzo, +7 authors, Michelino de Laurentiis.
Int J Mol Sci, 2020 Jul 02; 21(13). PMID: 32605126    Free PMC article.
Development of ErbB2-Targeting Liposomes for Enhancing Drug Delivery to ErbB2-Positive Breast Cancer.
Sho Ueno, Min Woo Kim, +3 authors, Ruda Lee.
Pharmaceutics, 2020 Jul 01; 12(6). PMID: 32599712    Free PMC article.
Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer.
Alexander Philipovskiy, Alok K Dwivedi, +5 authors, Sumit Gaur.
PLoS One, 2020 Sep 05; 15(9). PMID: 32886682    Free PMC article.
WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer.
Wei Wang, Urna Kansakar, +2 authors, Khalid Sossey-Alaoui.
Oncogenesis, 2020 Oct 06; 9(10). PMID: 33012785    Free PMC article.
Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies.
Gagan K Gupta, Amber L Collier, +13 authors, Amy H Tang.
Cancers (Basel), 2020 Aug 28; 12(9). PMID: 32846967    Free PMC article.