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« Back to Contents OVARIAN CANCER
LiFE re
Literature for ENYGO
Emerging molecular targeted therapies or early preclinical trials
in ovarian cancer
Editor Muhammad Rizki Yaznil Resensitisation of chemotherapy as a therapeutic approach
is the topic of the following articles:
Descriptive summary
T ang et al. [7] reported on a phase I study on CRM197, HB-EGF
Targeted therapy is still challenged by heterogeneity of the disease. inhibitor (Heparin-binding epidermal growth factor-like growth
factor) demonstrated that CRM197 could significantly reverse the
Tan et al. [1] described a database (CSIOVDB) with microarrays of resistance to paclitaxel in A2780/Taxol cells and xenografts which
3,431 ovarian cancers with molecular subtype, EMT status, clinico- over-express HB-EGF and EGFR.
pathological parameters and TCGA data. This database can enrich our
ability to find new and significant molecular targets for therapies. Inhibition of CDK1 with alsterpaullone may help to overcome re-
sistance to paclitaxel. Bae et al. [8] reported a reduction of tumour
The Ovarian Cancer Association Consortium [2] has analysed 2.8 growth upon paclitaxel subsequent to alsterpaullone treatment in
million SNPs with detailed chemotherapy and clinical follow-up a EOC xenograft model.
data. Three SNPs in three long non-coding RNAs (lncRNAs) were
associated with poor progression-free survival. One of these lies D asatinib is an orally administered ATP-competitive kinase
within a super-enhancer recently shown to be associated with poor inhibitor of the SFKs Src-family kinases and has shown substantial
prognosis in hepatocellular carcinoma. activity in EOC in preclinical studies, but not in phase II studies.
Pathak et al. [9] showed that of dasatinib and CX4945 (silmita-
miRNA is crucial for post-transcription regulation of gene expres- sertib), the first and only clinically relevant CK2 inhibitor, showed
sion. miRNAs are small (~22 bp) endogenous, non-protein-coding significant synergy across a panel of EOC cell lines in reducing
nucleotides that regulate gene expression. proliferation and increasing apoptosis.
Updates on this research topic: The development of a new agent and molecular target for
ovarian cancer:
R estoration of miRNA activity may represent a way to inhibit cancer
growth: Shields et al. [3] reported that miRNA mimic a toxicity screen p 53 is a tumour suppressor of paramount importance and p53
in a large diverse spectrum of EOC cell lines. miR-181 and miR-155 alterations are highly prevalent in ovarian cancer (>96 % HGSOC).
are toxic in chemoresistant ovarian cancer cells through dual modula- Soragni et al [10]. designed a cell-penetrating peptide, ReACp53,
tion of TGFβ and AKT signalling. miR-517a targets ARCN1. rescuing p53 function. Rescued p53 behaves similarly to its
wild-type counterpart in regulating target genes, reducing cell pro-
B oac et al. [4] identified 5 publically available micro-RNAs liferation and increasing cell death. Intraperitoneal administration
(miRNAs) associated with in vitro development of ovarian cancer decreases tumour proliferation and shrinks xenografts in vivo.
chemoresistance. These target multiple pathways, the majority
being associated with epithelial–mesenchymal transition (EMT). C atenin signalling is essential to developmental processes and
is deregulated in cancer. The R-spondin (RSPO) protein family
V an Jaarsveld et al. [5] found that miR-634 downregulation was enhance -catenin signalling. Chartier et al. [11] generated specific
associated with cisplatin resistance and overexpression of miR- monoclonal antibody RSPO antagonists and found that anti-RSPO
634 resensitised resistant ovarian cancer cell lines and patient de- treatment markedly inhibited tumour growth in human patient-de-
rived drug-resistant tumour cells to cisplatin. miR-634 interacted rived tumour xenograft models, either as single agents or in
with the cell cycle regulator CCND1, and the Ras-MAPK pathway. combination with chemotherapy.
C hen et al. [6] reports miR-509-3p downregulation in chemoresistant
EOC. Restoring of miR-509-3p may downregulate the expression of
XIAP (X-linked inhibitor of apoptosis) and inhibit EOC growth.
Resistance to chemotherapy is still a major problem in ovarian
cancer, especially in recurrent disease.
Continued on the next page
International Journal of Gynecological Cancer, Volume 26, Supplement #1 Page 15
