The impact of PI3K inhibitors on breast cancer cell and its tumor microenvironment

被引:38
|
作者
Qin, Hanjiao [1 ]
Liu, Linlin [1 ]
Sun, Shu [2 ]
Zhang, Dan [3 ]
Sheng, Jiyao [3 ]
Li, Bingjin [4 ]
Yang, Wei [4 ]
机构
[1] Jilin Univ, Hosp 2, Dept Radiotherapy, Changchun, Jilin, Peoples R China
[2] Changchun Univ Tradit Chinese Med, Affiliated Hosp, Changchun, Jilin, Peoples R China
[3] Jilin Univ, Hosp 2, Dept Hepatobiliary & Pancreat Surg, Changchun, Jilin, Peoples R China
[4] Jilin Univ, Hosp 2, Jilin Prov Key Lab Mol & Chem Genet, Changchun, Jilin, Peoples R China
来源
PEERJ | 2018年 / 6卷
关键词
Breast cancer; PI3K; Pathway inhibitors; Tumor microenvironment; Combination therapy; REGULATORY T-CELLS; PATHOLOGICAL COMPLETE RESPONSE; ESTROGEN-RECEPTOR-ALPHA; PIK3CA MUTATIONS; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL; 3-KINASE; PHOSPHOINOSITIDE; PHASE IB; ANTIESTROGEN RESISTANCE; P110-ALPHA ISOFORM;
D O I
10.7717/peerj.5092
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The phosphoinositide 3-kinase (PI3K) pathway shows frequent aberrant alterations and pathological activation in breast cancer cells. While PI3K inhibitors have not achieved expectant therapeutic efficacy in clinical trials, and several studies provide promising combination strategies to substantially maximize therapeutic outcomes. Besides its direct impact on regulating cancer cells survival, PI3K inhibitors are also demonstrated to have an immunomodulatory impact based on the tumor microenvironment. Inhibition of the leukocyte-enriched PI3K isoforms may break immune tolerance and restore cytotoxic T cell activity by reprogramming the tumor microenvironment. In addition, PI3K inhibitors have pleiotropic effects on tumor angiogenesis and even induce tumor vascular normalization. In this review, we discuss the mechanism of PI3K inhibitor suppression of breast cancer cells and modulation of the tumor microenvironment in order to provide further thoughts for breast cancer treatment.
引用
收藏
页数:27
相关论文
共 50 条
  • [31] The impact of PI3K/AKT inhibitor on the radiosensitization of breast cancer cells
    Fu, S
    Zeng, QW
    Sun, Y
    Zhang, Q
    Shao, YH
    Jian, GL
    [J]. RADIOTHERAPY AND ONCOLOGY, 2006, 78 : S93 - S93
  • [32] Clinical development of PI3K/AKT pathway inhibitors in breast cancer.
    Derynck, Mika
    [J]. MOLECULAR CANCER RESEARCH, 2018, 16 (08) : 22 - 22
  • [33] Treatment of Breast Cancer Using Multistage Delivery of PI3K/mTOR Inhibitors
    Blanco, E.
    Sangai, T.
    Martinez, J. O.
    Meric-Bernstam, F.
    Ferrari, M.
    [J]. CANCER RESEARCH, 2010, 70
  • [34] PI3K inhibitors as a backbone for combination treatments for breast and ovarian cancer.
    Wulf, Gerburg
    Konstantinopoulos, Panos
    Barry, William
    Sonzongi, Olmo
    Eismann, Julia
    Kucherlapati, Bose
    Matulonis, Ursula
    [J]. MOLECULAR CANCER RESEARCH, 2020, 18 (10) : 22 - 22
  • [35] Biomarkers of response and resistance to PI3K inhibitors in estrogen receptor-positive breast cancer patients and combination therapies involving PI3K inhibitors
    Brandao, M.
    Caparica, R.
    Eiger, D.
    de Azambuja, E.
    [J]. ANNALS OF ONCOLOGY, 2019, 30 : 27 - 42
  • [36] Phytochemicals as PI3K/Akt/mTOR Inhibitors and Their Role in Breast Cancer Treatment
    Narayanankutty, Arunaksharan
    [J]. RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY, 2020, 15 (03) : 188 - 199
  • [37] What is the potential of using PI3K inhibitors in the management of breast cancer in the clinic?
    Mayer, Ingrid A.
    [J]. BREAST CANCER MANAGEMENT, 2014, 3 (04) : 345 - 357
  • [38] First PI3K Inhibitor for Breast Cancer
    Voelker, Rebecca
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2019, 322 (01): : 19 - 19
  • [39] PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations
    Chung, Wei-Pang
    Huang, Wei-Lun
    Lee, Chun-Hui
    Hsu, Hui-Ping
    Huang, Wan-Ling
    Liu, You-Yu
    Su, Wu-Chou
    [J]. AMERICAN JOURNAL OF CANCER RESEARCH, 2022, 12 (07): : 3067 - +
  • [40] Double PIK3CA mutations in cis enhance PI3Kα oncogene activation and sensitivity to PI3Kα inhibitors in breast cancer
    Vasan, N.
    Razavi, P.
    Johnson, J. L.
    Shao, H.
    Reznik, E.
    Smith, M. L.
    Sebra, R.
    Cantley, L. C.
    Scaltriti, M.
    Baselga, J.
    [J]. ANNALS OF ONCOLOGY, 2019, 30 : 1 - 1