August 2024 SOCRA Source Journal - Journal - Page 47
TABLE 2
TNBC biomarker and molecular therapeutic targets
TNBC Biomarkers
The Molecular Targets
Epidermal Growth Factor Receptor (EGFR)
Marker of cellular proliferation, angiogenesis,
metastasis and apoptosis inhibition
Vascular Endothelial Growth Factor (VEGF)
Proliferation and maintains the integrity of the cell
C-kit and Basal Cytokeratin
Stimulates survival and differentiation and induces
invasiveness in the cancerous cell
P53
Cell cycle regulation and tumour apoptosis
hKi67
A cellular proliferation marker
PARP
A family of cell signaling enzymes.
Hsp90
A cellular chaperone
COX2
In昀氀ammatory expression protein
TK
Cell grow and differentiate protein
Mtor
Association with a poor response to treatment
and death through predilection
for visceral lung and brain metastasis (Kennecke et al. 2010).
Patients with TNBC have a
highest risk of recurrence
and metastasis (Foulkes et
al. 2010). Different targeted
treatment strategies have
been investigated, but none
are currently recorded bene昀椀t,
for example, Bevacizumab,
a VEGF- targeting anti-body
was granted accelerated
FDA approval with weekly
paclitaxel for 昀椀rst line treatment
of metastatic breast cancer,
however, this treatment was
later revoked after following up
phase III clinical trials. Preclinical
studies have implicated AR as
a potential tumour suppressor
in ER–positive breast cancer
with anti-proliferation effects
owing to the cross talk between
the steroid receptor signaling
pathways. The reason is AR is
activated by testosterone and
dihydrotestosterone, which
is involved in the function of
multiple female organs, such as
the reproduction tract as well as,
bones, kidneys, and muscles.
Moreover, testosterone and
dihydrotestosterone act as
prohormones of estradiol and
bind directly to AR. The result
of binding is the translocation of
the receptor to the nucleus and
a binding to the target genes
and transcriptional activation
(Zhu et al. 1997). Moreover,
clinical data analysis has shown
that the androgen signaling
pathway plays an essential
role in the development of
normal and malignant breast
tissue. Epidemiology studies
have suggested that increased
levels of androgen receptor are
associated with an increased
risk of breast cancer (Birrell et al.
2007, Wilson et al. 1981, Hickey
et al. 2012).
A considerable amount of
literature has been published
on Antibody-Drug Conjugates
(ADC). These studies have
discovered that several ADC are
encouraging the action in triple
negative breast cancer such as,
Sacituzumab govitecan (IMMU132) is an Ab–SN-38 conjugate
targeting TROP2, which is
activated in most studied tumour
specimens (approximately
88%). These were moderately
to strongly positive for Trop2 by immunohistochemistry
research and clearly showed that
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