The Innovation,
Journal Year:
2021,
Volume and Issue:
2(2), P. 100103 - 100103
Published: April 3, 2021
The
discovery
that
mutations
in
the
EGFR
gene
are
detected
up
to
50%
of
lung
adenocarcinoma
patients,
along
with
development
highly
efficacious
epidermal
growth
factor
receptor
(EGFR)
tyrosine
kinase
inhibitors
(TKIs),
has
revolutionized
treatment
this
frequently
occurring
malignancy.
Indeed,
clinical
success
these
TKIs
constitutes
a
critical
milestone
targeted
cancer
therapy.
Three
generations
EGFR-TKIs
currently
approved
for
mutation-positive
non-small
cell
(NSCLC).
first-generation
include
erlotinib,
gefitinib,
lapatinib,
and
icotinib;
second-generation
ErbB
family
blockers
afatinib,
neratinib,
dacomitinib;
whereas
osimertinib,
by
FDA
on
2015,
is
third-generation
TKI
targeting
harboring
specific
mutations.
Compared
first-
TKIs,
display
significant
advantage
terms
patient
survival.
For
example,
median
overall
survival
NSCLC
patients
receiving
osimertinib
reached
38.6
months.
Unfortunately,
however,
like
other
therapies,
new
mutations,
as
well
additional
drug-resistance
mechanisms
emerge
rapidly
after
treatment,
posing
formidable
obstacles
therapeutics
aimed
at
surmounting
chemoresistance.
In
review,
we
summarize
molecular
underlying
resistance
ongoing
efforts
address
overcome
We
also
discuss
current
status
fourth-generation
inhibitors,
which
great
value
overcoming
appear
have
greater
therapeutic
benefits
clinic.
Molecular Oncology,
Journal Year:
2020,
Volume and Issue:
14(3), P. 539 - 555
Published: Jan. 4, 2020
Malignant
tumors,
including
colorectal
cancer
(CRC),
usually
rely
on
ATP
generation
through
aerobic
glycolysis
for
both
rapid
growth
and
chemotherapy
resistance.
The
M2
isoform
of
pyruvate
kinase
(PKM2)
has
a
key
role
in
catalyzing
glycolysis,
PKM2
expression
varies
even
within
single
tumor.
In
this
study,
we
confirmed
that
is
heterogeneous
CRC
cells,
namely
high
oxaliplatin-resistant
cells
but
relatively
low
sensitive
found
chemoresistant
had
enhanced
production.
addition,
report
PKM2-dependent
mechanism
which
chemosensitive
may
gradually
transform
into
cells.
circular
RNA
hsa_circ_0005963
(termed
ciRS-122
study),
was
determined
to
be
sponge
the
PKM2-targeting
miR-122,
positively
correlated
with
chemoresistance.
vitro
vivo
studies
showed
exosomes
from
delivered
thereby
promoting
drug
resistance
miR-122
sponging
upregulation.
Moreover,
si-ciRS-122
transported
by
could
suppress
reverse
oxaliplatin
regulating
ciRS-122-miR-122-PKM2
pathway
vivo.
Exosomes
derived
transfer
across
promote
reduce
susceptibility
This
intercellular
signal
delivery
suggests
potential
novel
therapeutic
target
establishes
foundation
future
clinical
applications
drug-resistant
CRC.
Drug Resistance Updates,
Journal Year:
2021,
Volume and Issue:
59, P. 100796 - 100796
Published: Dec. 1, 2021
Driver
mutations
promote
initiation
and
progression
of
cancer.
Pharmacological
treatment
can
inhibit
the
action
mutant
protein;
however,
drug
resistance
almost
invariably
emerges.
Multiple
studies
revealed
that
cancer
is
based
upon
a
plethora
distinct
mechanisms.
Drug
occur
in
same
protein
or
different
proteins;
as
well
pathway
parallel
pathways,
bypassing
intercepted
signaling.
The
dilemma
clinical
oncologist
facing
not
all
genomic
alterations
tumor
microenvironment
facilitate
cell
proliferation
are
known,
neither
likely
to
metastasis.
For
example,
common
KRas
