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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

Descriptive summary (cont.) A little insight on “double edge sword” immunology and
immunotherapy in ovarian cancer:
T etraspanins (TSPANs) are a family of small proteins that are
parts of a specific signalling platform involved in many important C arbotti et al. [16] described how IL-27 inhibits the growth and
cellular functions and malignant processes. Park et al. [12] found invasiveness of different cancers and therefore represents a
that TSPAN8 is overexpressed in about 52 % (14/27) of EOC tis- potential anti-tumour agent. However, it also induces IDO or PD-L1
sues and was correlated with poor survival. It was a key regulator expression through STAT1 and STAT3 tyrosine phosphorylation.
of EOC cell invasion and monotherapy with TSPAN8-blocking Immune-enhancing monoclonal antibodies (mAbs) that target
antibody showed significant reduction of the incidence of EOC immune checkpoints such as anti-PD-1 and anti-PD-L1 currently
metastasis without severe toxicity. are being studied in EOC.

S tope et al. [13] reviewed the role of HSP (heat shock proteins)
in ovarian cancer. HSPs were characterised as molecular chaper-
ones and perform crucial roles in folding/unfolding, turnover, and
transport of proteins as well as in the assembly of multiprotein
complexes. HSP90 stabilises the mutant p53 protein in cancer
cells. Pharmacologic inhibition of HSP90 destroys the complex
between HSP90 and mutant p53 protein, thereby liberating mutant
p53 and causing cytotoxicity in p53 mutant cancer cells in culture
and in xenografts. Another European clinical trial studied the
second-generation HSP90 inhibitor ganetespib (Synta Pharmaceu-
tical, Lexington, MA, USA) in combination with weekly paclitaxel
in mainly HGS platinum-resistant ovarian cancer patients.

T he prognosis of advanced CCC is very poor, primarily because
of its resistance to platinum-based chemotherapy. Matsuzaki et
al. [14] highlighted several potential therapeutic targets in these
patients based on molecular pathways.

Repurposing of drugs:

M onensin (rumensin) is a polyether ionophore antibiotic secreted
by the bacteria Streptomyces cinnamonensis. Monensin acted
synergistically with EGFR inhibitors and oxaliplatin to inhibit cell
proliferation and induce apoptosis of ovarian cancer cells. Xen-
ograft studies showed that monensin effectively inhibits tumour
growth by suppressing cell proliferation through targeting EGFR
signalling (Deng et al.; 15).

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International Journal of Gynecological Cancer, Volume 26, Supplement #1