TY - JOUR
T1 - The tumor microenvironment as driver of stemness and therapeutic resistance in breast cancer
T2 - New challenges and therapeutic opportunities
AU - Mehraj, Umar
AU - Ganai, Rais A.
AU - Macha, Muzafar A
AU - Hamid, Abid
AU - Zargar, Mohammed A.
AU - Bhat, Ajaz A.
AU - Nasser, Mohd Wasim
AU - Haris, Mohammad
AU - Batra, Surinder K.
AU - Alshehri, Bader
AU - Al-Baradie, Raid Saleem
AU - Mir, Manzoor A.
AU - Wani, Nissar Ahmad
N1 - Funding Information:
The work was supported by a Ramalinga Swami Fellowship, Grant No. BT/HRD/35/02/2006, to Nissar Ahmad Wani from the Department of Biotechnology (DBT), Ministry of Science & Technology, New Delhi.
Funding Information:
Umar Mehraj is a recipient of a junior research fellowship (JRF) from UGC-CSIR, Govt. of India. Muzafar Ahmad Macha and Rais A. Ganai are recipients of a Ramanujan Fellowship from the Science & Engineering Research Board (SERB), Department of Science and Technology, Govt. of India, New Delhi. Figure was designed using BioRender.com web resource.
Publisher Copyright:
© 2021, Springer Nature Switzerland AG.
PY - 2021/12
Y1 - 2021/12
N2 - Background: Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. The tumor microenvironment (TME), comprising cellular components, such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and adipocytes, and noncellular components such as extracellular matrix (ECM), has been recognized as a critical contributor to the development and progression of BC. The interplay between TME components and cancer cells promotes phenotypic heterogeneity, cell plasticity and cancer cell stemness that impart tumor dormancy, enhanced invasion and metastasis, and the development of therapeutic resistance. While most previous studies have focused on targeting cancer cells with a dismal prognosis, novel therapies targeting stromal components are currently being evaluated in preclinical and clinical studies, and are already showing improved efficacies. As such, they may offer better means to eliminate the disease effectively. Conclusions: In this review, we focus on the evolving concept of the TME as a key player regulating tumor growth, metastasis, stemness, and the development of therapeutic resistance. Despite significant advances over the last decade, several clinical trials focusing on the TME have failed to demonstrate promising effectiveness in cancer patients. To expedite clinical efficacy of TME-directed therapies, a deeper understanding of the TME is of utmost importance. Secondly, the efficacy of TME-directed therapies when used alone or in combination with chemo- or radiotherapy, and the tumor stage needs to be studied. Likewise, identifying molecular signatures and biomarkers indicating the type of TME will help in determining precise TME-directed therapies.
AB - Background: Breast cancer (BC), the second most common cause of cancer-related deaths, remains a significant threat to the health and wellness of women worldwide. The tumor microenvironment (TME), comprising cellular components, such as cancer-associated fibroblasts (CAFs), immune cells, endothelial cells and adipocytes, and noncellular components such as extracellular matrix (ECM), has been recognized as a critical contributor to the development and progression of BC. The interplay between TME components and cancer cells promotes phenotypic heterogeneity, cell plasticity and cancer cell stemness that impart tumor dormancy, enhanced invasion and metastasis, and the development of therapeutic resistance. While most previous studies have focused on targeting cancer cells with a dismal prognosis, novel therapies targeting stromal components are currently being evaluated in preclinical and clinical studies, and are already showing improved efficacies. As such, they may offer better means to eliminate the disease effectively. Conclusions: In this review, we focus on the evolving concept of the TME as a key player regulating tumor growth, metastasis, stemness, and the development of therapeutic resistance. Despite significant advances over the last decade, several clinical trials focusing on the TME have failed to demonstrate promising effectiveness in cancer patients. To expedite clinical efficacy of TME-directed therapies, a deeper understanding of the TME is of utmost importance. Secondly, the efficacy of TME-directed therapies when used alone or in combination with chemo- or radiotherapy, and the tumor stage needs to be studied. Likewise, identifying molecular signatures and biomarkers indicating the type of TME will help in determining precise TME-directed therapies.
KW - Breast cancer
KW - Cancer stemness
KW - Cancer-associated fibroblasts
KW - Immunotherapy
KW - Targeted therapeutics
KW - Tumor microenvironment
KW - Tumor-associated macrophages
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U2 - 10.1007/s13402-021-00634-9
DO - 10.1007/s13402-021-00634-9
M3 - Review article
C2 - 34528143
AN - SCOPUS:85114927246
VL - 44
SP - 1209
EP - 1229
JO - Cellular oncology (Dordrecht)
JF - Cellular oncology (Dordrecht)
SN - 2211-3428
IS - 6
ER -