TY - JOUR
T1 - Targeting the microenvironment in high grade serous ovarian cancer
AU - Nwani, Nkechiyere G.
AU - Sima, Livia E.
AU - Nieves-Neira, Wilberto
AU - Matei, Daniela
N1 - Funding Information:
Funding: This research was supported through funding from US Department of Veterans’ Affairs, BX000792-06 and the Department of Defense W81XWH-17-1-0141 (to Daniela Matei), and the National Cancer Institute Training Grant T32 CA070085 (to Nkechiyere G. Nwani).
Funding Information:
This research was supported through funding from US Department of Veterans’ Affairs, BX000792-06 and the Department of Defense W81XWH-17-1-0141 (to Daniela Matei), and the National Cancer Institute Training Grant T32 CA070085 (to Nkechiyere G. Nwani).
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/8/10
Y1 - 2018/8/10
N2 - Cancer–stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulated therapeutically. Results of emerging preclinical and clinical trials testing TME-modulating therapeutics for the treatment of OC are highlighted.
AB - Cancer–stroma interactions play a key role in cancer progression and response to standard chemotherapy. Here, we provide a summary of the mechanisms by which the major cellular components of the ovarian cancer (OC) tumor microenvironment (TME) including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This profile is correlated with clinical outcomes and can be a target for therapy. Accumulation of malignant ascites in the peritoneal cavity allows for secreted factors to fuel paracrine and autocrine circuits that augment cancer cell proliferation and invasiveness. Adhesion of cancer cells to the mesothelial matrix promotes peritoneal tumor dissemination and represents another attractive target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is permissive for tumor growth and can be modulated therapeutically. Results of emerging preclinical and clinical trials testing TME-modulating therapeutics for the treatment of OC are highlighted.
KW - Angiogenesis
KW - High-grade serous ovarian cancer
KW - Immune response
KW - Metastasis
KW - Therapeutic targeting strategies
KW - Tumor microenvironment
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U2 - 10.3390/cancers10080266
DO - 10.3390/cancers10080266
M3 - Review article
C2 - 30103384
AN - SCOPUS:85051411693
SN - 2072-6694
VL - 10
JO - Cancers
JF - Cancers
IS - 8
M1 - 266
ER -
