Tumour Microenvironment Stress Promotes the Development of Drug Resistance

被引:41
|
作者
Seebacher, Nicole A. [1 ]
Krchniakova, Maria [2 ,3 ]
Stacy, Alexandra E. [4 ]
Skoda, Jan [2 ,3 ]
Jansson, Patric J. [4 ,5 ]
机构
[1] Univ Oxford, Dept Oncol, Oxford OX3 9DU, England
[2] Masaryk Univ, Fac Sci, Dept Expt Biol, Brno 62500, Czech Republic
[3] St Annes Univ Hosp, Int Clin Res Ctr, Brno 65691, Czech Republic
[4] Univ Sydney, Sch Med Sci, Fac Med & Hlth, Canc Drug Resistance & Stem Cell Program, Camperdown, NSW 2006, Australia
[5] Univ Sydney, Kolling Inst, Fac Med & Hlth, Bill Walsh Translat Canc Res Lab, St Leonards, NSW 2065, Australia
关键词
tumour microenvironmental stress; drug resistance; reactive oxygen species; cancer stem cells; CANCER-ASSOCIATED FIBROBLASTS; INDUCIBLE FACTOR 1-ALPHA; HUMANIZED MONOCLONAL-ANTIBODY; I DOSE-ESCALATION; CELL LUNG-CANCER; CD4(+) T-CELLS; FACTOR-KAPPA-B; OXIDATIVE STRESS; BREAST-CANCER; UP-REGULATION;
D O I
10.3390/antiox10111801
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.
引用
收藏
页数:32
相关论文
共 50 条
  • [41] Endoplasmic reticulum stress in the development of multiple myeloma and drug resistance
    Nikesitch, Nicholas
    Lee, James M.
    Ling, Silvia
    Roberts, Tara Laurine
    [J]. CLINICAL & TRANSLATIONAL IMMUNOLOGY, 2018, 7 (01):
  • [42] Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance
    Khalaf, Khalil
    Hana, Doris
    Chou, Jadzia Tin-Tsen
    Singh, Chandpreet
    Mackiewicz, Andrzej
    Kaczmarek, Mariusz
    [J]. FRONTIERS IN IMMUNOLOGY, 2021, 12
  • [43] The Retinoblastoma Tumor Microenvironment Contributes to Drug Resistance
    Wilson, Matthew W.
    Goldsmith, Zachary K.
    Brouner, M. Robert
    Brennan, Rachel C.
    King, Benjamin A.
    Morales-Tirado, Vanessa Marie
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2019, 60 (09)
  • [44] The microenvironment is the key determinant of melanoma drug resistance
    Haass, N. K.
    Smalley, K. S.
    Herlyn, M.
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 : 145 - 145
  • [45] Tumor microenvironment and drug resistance hematologic malignancies
    Li, Zhi-Wei
    Dalton, William S.
    [J]. BLOOD REVIEWS, 2006, 20 (06) : 333 - 342
  • [46] The tumor microenvironment as a determinant of drug response and resistance
    Dalton, WS
    [J]. DRUG RESISTANCE UPDATES, 1999, 2 (05) : 285 - 288
  • [47] Flotillin-1 is a prognostic biomarker for glioblastoma and promotes cancer development through enhancing invasion and altering tumour microenvironment
    Wang, Ran
    Chen, Zhikang
    Zhang, Yi
    Xiao, Shihan
    Zhang, Wuming
    Hu, Xianqin
    Xiao, Qun
    Liu, Qing
    Wang, Xiangyu
    [J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2023, 27 (03) : 392 - 402
  • [48] A Hypercoagulant Tumour Microenvironment Promotes Breast Cancer Progression, with Effects Inhibited by Anticoagulants
    Blower, E.
    Castle, J.
    Santiago-Gomez, A.
    Clarke, R.
    Kirwan, C.
    [J]. JOURNAL OF PATHOLOGY, 2021, 255 : S4 - S4
  • [49] Carbon substrates promotes stress resistance and drug tolerance in clinical isolates of Candida tropicalis
    Khamrai, Arpita
    Paul, Saikat
    Rudramurthy, Shivaprakash M.
    Ghosh, Anup K.
    [J]. ARCHIVES OF MICROBIOLOGY, 2024, 206 (06)
  • [50] Oxidative stress promotes myofibroblast differentiation and tumour spreading
    Toullec, A.
    Gerald, D.
    Despouy, G.
    Bourachot, B.
    Stern, M.
    Dubois, T.
    Sastre-Garau, X.
    Delattre, O.
    Vincent-Salomon, A.
    Mechta-Grigoriou, F.
    [J]. EJC SUPPLEMENTS, 2010, 8 (03): : 124 - 124