TY - JOUR

T1 - Kinase Inhibitors in the Treatment of Ovarian Cancer

T2 - Current State and Future Promises

AU - Skorda, Aikaterini

AU - Bay, Marie Lund

AU - Hautaniemi, Sampsa

AU - Lahtinen, Alexandra

AU - Kallunki, Tuula

N1 - Funding Information: This research was funded by the Research and Innovation programme under grant agreement No 965193 for DECIDER (S.H and T.K) and by Grosserer Alfred Nielsen og Hustrus Fond and Fabrikant Chas. Otzen´s Fond (T.K.). Open access funding provided by University of Helsinki. Publisher Copyright: © 2022 by the authors.

PY - 2022

Y1 - 2022

N2 - Ovarian cancer is the deadliest gynecological cancer, the high-grade serous ovarian carcinoma (HGSC) being its most common and most aggressive form. Despite the latest therapeutical advancements following the introduction of vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors and poly-ADP-ribose-polymerase (PARP) inhibitors to supplement the standard platinum- and taxane-based chemotherapy, the expected overall survival of HGSC patients has not improved significantly from the five-year rate of 42%. This calls for the development and testing of more efficient treatment options. Many oncogenic kinase-signaling pathways are dysregulated in HGSC. Since small-molecule kinase inhibitors have revolutionized the treatment of many solid cancers due to the generality of the increased activation of protein kinases in carcinomas, it is reasonable to evaluate their potential against HGSC. Here, we present the latest concluded and on-going clinical trials on kinase inhibitors in HGSC, as well as the recent work concerning ovarian cancer patient organoids and xenograft models. We discuss the potential of kinase inhibitors as personalized treatments, which would require comprehensive assessment of the biological mechanisms underlying tumor spread and chemoresistance in individual patients, and their connection to tumor genome and transcriptome to establish identifiable subgroups of patients who are most likely to benefit from a given therapy.

AB - Ovarian cancer is the deadliest gynecological cancer, the high-grade serous ovarian carcinoma (HGSC) being its most common and most aggressive form. Despite the latest therapeutical advancements following the introduction of vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors and poly-ADP-ribose-polymerase (PARP) inhibitors to supplement the standard platinum- and taxane-based chemotherapy, the expected overall survival of HGSC patients has not improved significantly from the five-year rate of 42%. This calls for the development and testing of more efficient treatment options. Many oncogenic kinase-signaling pathways are dysregulated in HGSC. Since small-molecule kinase inhibitors have revolutionized the treatment of many solid cancers due to the generality of the increased activation of protein kinases in carcinomas, it is reasonable to evaluate their potential against HGSC. Here, we present the latest concluded and on-going clinical trials on kinase inhibitors in HGSC, as well as the recent work concerning ovarian cancer patient organoids and xenograft models. We discuss the potential of kinase inhibitors as personalized treatments, which would require comprehensive assessment of the biological mechanisms underlying tumor spread and chemoresistance in individual patients, and their connection to tumor genome and transcriptome to establish identifiable subgroups of patients who are most likely to benefit from a given therapy.

KW - clinical trials

KW - high-grade serous ovarian carcinoma

KW - kinase inhibitor

KW - patient-derived tumor organoids

KW - patient-derived xenografts

KW - personalized medicine

U2 - 10.3390/cancers14246257

DO - 10.3390/cancers14246257

M3 - Review

C2 - 36551745

AN - SCOPUS:85144847322

VL - 14

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 24

M1 - 6257

ER -