Cancer Letters 233 (2006) 1–9

www.elsevier.com/locate/canlet

Mini-review

Ether à go-go potassium channels and cancer

Javier Camacho*
Pharmacology Section, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional,
Avenida Instituto Politécnico Nacional 2508, México, DF 07360, México

Received 10 February 2005; accepted 14 February 2005

Abstract
Ion channels play important roles in health and disease. In the last few years, an interesting relationship between potassium
channels and cancer has evolved. Especially, members of the ether à go-go (EAG) potassium channels family have gained
interest as research tools for detection and therapy of different cancers. This review will summarize most of the findings relating
EAG channels and cancer, focusing on mRNA expression in tissues, oncogenic properties, modulation and pharmacology.
Plausible scenarios on the cellular mechanisms of EAG oncogenicity will be discussed.
q 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Cancer; Tumor markers; Cervical cancer; Ion channels; Ether à go-go; Herg; Proliferation; Epsin; Human papilloma virus;
Tamoxifen; Patch-clamp; Potassium channels; Hypoxia; Von hippel-lindau protein

1. Introduction signals vary from voltage and neurotransmitters to pH

Ion channels are membrane proteins governing
massive ion fluxes through the cells and participating
in many and diverse physiological events such as
excitability, contraction, cell cycle progression and
metabolism [1] both in health and disease. Several
channelopathies have been described and many of
these proteins are therapeutic targets, highlighting the
physiological relevance of ion channels [2]. In
addition to leak channels, which are opened at resting
membrane potential, there is a quite diverse group of
channels needing a special signal to be gated. Gating
* Tel.: C52 55 50613800x5416; fax: C52 55 53430106.
E-mail address: fcamacho@cinvestav.mx.
and temperature and are usually specific for a type of
channel [3]. Several ion channels have been related to
cell proliferation and/or cancer including calcium,
chloride and sodium channels [4–6]; however, the ion
channels most commonly related to cell proliferation
and cancer are the potassium channels; actually some
excellent general reviews on potassium channels and
cell proliferation have been recently published [7–9].
This review focus on the family of voltage-gated
potassium channels ether à go-go (EAG) and its
interesting relationship to cancer. Because of their
oncogenic properties, distribution, modulation and
pharmacology, EAG channels have gained interest as
potential diagnostic markers and membrane thera-
peutic targets for cancer.

0304-3835/$ - see front matter q 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.canlet.2005.02.016
2 J. Camacho / Cancer Letters 233 (2006) 1–9
2. Ether à go-go channels
In 1969, several mutants from the fruit fly
Drosophila melanogaster were produced following
the treatment of adult males by ethyl methane
sulfonate [10]. The mutants presented shaking of the
legs under ether anesthesia and independent gene loci
were found to be involved. One of these mutants
exhibited a slow and rhythmic leg-shaking behaviour;
the locus involved was then named ether à go-go
(eag).
Further evidences including the observation that
eag mutants presented a high frequency of spon-
taneous action potentials and enhanced transmitter
release in motor neurons, and the comparison of eag
sequence with other genes [11,12], suggested that eag
might encode for a protein involved in cellular
excitability, namely, a potassium channel. It was in
1993 that expression studies in oocytes demonstrated
that Drosophila eag encodes a voltage-gated potass-
ium channel [13]. Homology screening helped to
identify other two sequences closely related to eag:
the eag-related gene (erg) and the eag-like gene (elk);
thus the EAG channels family comprises three
subfamilies: EAG, ERG and ELK [14]. Two members
for the eag subfamily, three for erg and two for elk are
differentially expressed in different species including
rat, bovine and humans [reviewed in Ref. [15]]. In the
present review, ‘EAG’ will refer to members belong-
ing to the EAG channels family; and only those
channels involved in cell proliferation and/or cancer
will be discussed, it is ‘eag1’ (from the eag subfamily)
and ‘erg’ channels.
Distribution of EAG in normal tissues depends on
the subfamily. Erg channels are ubiquitous; tran-
scripts have been found in heart, brain, kidney, liver,
testis, uterus and prostate, among other sites
[reviewed in Ref. [16]]. Eag1 has a more restricted
distribution, it has been found almost exclusively in
brain, slightly in placenta and transiently in myoblasts
[17,18]; in fact, this restricted distribution in normal
tissues is one of the most attractive features of eag1 as
a potential tumor marker.
EAG channels form tetramers, each monomeric
subunit has six putative transmembrane domains
including the voltage sensor (a segment enriched in
positively charged amino-acids) and its intracellular
C- and N-terminus with a Per-Arnt-Sim (PAS)
domain in the former and a cyclic nucleotide binding
domain in the latter [reviewed in Ref. [15]]. PAS
domain has been suggested to be an oxygen sensor
[19], actually, EAG channels are modulated by
hypoxia or hypoxia-related proteins, as will be
discussed later.
Particular voltage-dependent properties of eag and
erg channels as well as pharmacological tools
[reviewed in Ref. [15]] allow to identify endogenous
EAG mediated currents. As expected for voltage-
gated channels, different roles have been described to
members of the EAG family in excitable cells. Erg
channels have a major role in the repolarization phase
of the cardiac action potential; mutations in this gene
are responsible for the long Q-T syndrome 2 (LQT2)
in humans and the channels are targeted by several
anti-arrhythmic drugs [reviewed in Ref. [20]]. In
addition, during a train of action potentials, a role in
spike-frequency adaptation has been suggested for erg
[21]. In the case of the eag1, known physiological
roles in normal cells are limited to human myoblasts
differentiation [22] and will be described below.
Specific roles for eag1 have not been described in
nervous system, despite its major expression in brain.
Interestingly, different experimental approaches
have related eag1 and erg channels to cell cycle and
cellular transformation, suggesting them as potential
diagnose markers and therapeutic targets for cancer.
3. EAG channels, cell-cycle and cancer
3.1. Cell-cycle and EAG
Indicative data that EAG might be related to or
modulated during cell-cycle appeared when electro-
physiological studies showed that currents with
biophysical and pharmacological properties resem-
bling those of erg channels were present in neuro-
blastoma cell lines; the voltage-dependent properties
of such currents varied widely in unsynchronized cells
but the variability was greatly reduced when the cells
were synchronized in the G1 phase of the cell cycle
[23].
Later on, Walter Stühmer’s group described for the
first time that a channel with a defined molecular
entity, namely eag1, was ‘cell cycle-sensitive’. Frog
oocytes arrested in G2 phase are commonly used for
 J. Camacho / Cancer Letters 233 (2006) 1–9
cell-cycle studies and expression of exogenous
proteins; addition of progesterone to the oocytes
induces cell-cycle progression reentering the cells into
the meiotic phase [24,25]. Stühmer’s group expressed
rat eag1 channels in the oocytes and found that
channel activity was down-regulated in the presence
of progesterone; because this effect was also observed
when injecting the Mitosis Promoting Factor even in
the absence of progesterone, the conclusion was that
eag1 was modulated in a cell-cycle dependent manner
[26]. Cloning of human eag1 was soon reported and a
physiological role in a cell-cycle-related event
described [17]. In human myoblasts, cell-cycle is
arrested by cell fusion and membrane hyperpolariz-
ation is needed. H-eag1 is transiently expressed in
myoblasts slightly before fusion providing an early
hyperpolarization, then eag expression decreases and
it is not expressed in the multinucleate skeletal muscle
cell [22]. Properties of eag1 channels during cell-
cycle were then studied in detail; during M-phase, rat
and h-eag1 channels expressed in a cell line become
more selective to potassium ions, are sensitive to
blockage by intracellular sodium and display a
smaller current density in comparison to G1, S or
G2 phases [27,28]; this cell-cycle modulation was
suggested to be determined by cytoskeletal elements
proposing that eag1 channels might be modulated in
other cellular events in which cytoskeletal rearrange-
ments occur, as in migration of cancer cells. It was
also observed that erg is rapidly turned on in normal
CD34C cells from peripheral blood upon induction of
the mitotic cycle by cytokines/growth factors [33].
Different tumor cell lines and primary human
cancer cells have been used for expression, modu-
lation, and pharmacological EAG studies creating a
new atmosphere in the study of cancer and ion
channels. Following, major findings on EAG and
cancer are described and summarized in Table 1.
3.2. EAG and cancer
There are two initial papers representing the
milestones of the link cancer-EAG. The first report
was communicated by Enzo Wanke’s group. They
showed that human erg transcripts were expressed in
tumor cell lines from different histogenesis including
rhabdomyosarcoma, neuroblastoma, mammary gland
adenocarcinoma and monoblastic leukemia cell lines
3
[29], and suggested h-erg channel activity as a
selective advantage for cancer cells. Ischemic con-
ditions lead to failure of the NaC/KC pump inducing
cellular potassium loss, which is a prerequisite for
apoptosis; the authors suggested that h-erg channels
might provide the hyperpolarization needed to avoid
such potassium loss preventing the cells from entering
the apoptotic pathway.
The second report is a landmark in ion channel
research and was communicated by Stühmer’s group.
They demonstrated that eag1 posses oncogenic
properties. Cell lines transfected with eag1 acquire
properties of cancerous cells, namely, they lose cell-
contact inhibition, are able to grow in very low serum-
concentrations and, noteworthy, induce formation of
aggressive tumors when injected into immune-
depressed mice [18]. Moreover, in contrast to its
restricted distribution in normal tissues (mainly in
brain, slightly in placenta and transiently in myo-
blasts) they found that eag1 was expressed in several
human somatic cancer cell lines including HeLa,
MCF-7 and SHSY-5Y, from carcinoma of the cervix,
breast tumor and neuroblastoma, respectively. The
immediately arising question was whether eag1
expression in tumor cells was a consequence of the
abnormal growth or if the channels were necessary for
cell proliferation. Antisense experiments against
h-eag1 decreased significantly DNA synthesis in the
tumor cell lines mentioned above, suggesting that
eag1 channels are important in the proliferation of the
tumor cells lines. In a following communication, the
same group reported that inhibition of eag1 (either
expression or channel function) by small molecule,
blocking antibody or short interfering RNA led to a
reduction in DNA synthesis and proliferation in
several human tumor cell lines [30]. Therefore,
h-eag1 is considered as a potential tumor marker
and therapeutic target for cancer.
Further investigations have shown EAG expression
and/or channel activity in additional tumor cell lines
including melanoma, neuroblastoma and rhabdomyo-
sarcoma for eag1 [31,32,42], and hematopoietic
(Burkitt’s lymphoma, chronic myelogenous leukemia,
acute lymphoblastic leukemia and acute promyelocy-
tic leukemia), uterine cancer, retinoblastoma, mam-
mary adenocarcinoma and colon cancer cells for erg
[33–36,42].
4 J. Camacho / Cancer Letters 233 (2006) 1–9

Table 1
Major findings relating cancer to human EAG channels

Channel Finding Refs.

Eag1 Displays oncogenic potential. Induces aggressive tumor formation in SCID mice. mRNA expressed in [17,18,30]
several somatic tumor cell lines including HeLa, MCF-7 and SHSY-5Y, but in normal tissues only in
brain, placenta and transiently in myoblasts. Inhibition of expression or channel activity by different
experimental approaches decreased cell proliferation in tumor cell lines
Transcript present in melanoma and neuroblastoma cells and channel activity inhibited by imipramine [31,32,52]
mRNA expressed in gliomas depending on the malignancy of the tumor [39]
mRNA expression in 100% of cervical cancer. Channel activity found in cancer cells. Expression in some [40]
normal cervical samples (from patients with negative pap smears) suggested as potential early indicator
of tumor development. Probably associated to HPV infection
Inhibited by the hypoxia-related and tumor suppressor gene von Hippel-Lindau in neuroblastoma cells [45]
Erg mRNA expression and channel activity in several tumor cell lines from different histogenesis including [29,33–35,42]
neuroblastoma, rhabdomyosarcoma, hemopoietic, retinoblastoma, mammary adenocarcinoma, uterine
and colon cancer cells. Suggested as an advantage for tumor cells by preventing apoptosis
More frequently expressed in human endometrial cancer as compared to non-cancerous endometrium [33,36]
and not found in endometrial hyperplasia. Constitutively activated in neoplastic hematopoietic cells
while turned-off in normal cells
mRNA expression in gliomas and channel activity present in lactotrophs from prolactinoma tissue [38,39]
mRNA expression and channel activity in primary colon cancer with a higher incidence in metastatic [36]
cancers. No expression found in normal colonic mucosa or adenomas. Suggested as a potential
prognostic factor
Modulated by hypoxic conditions and Src tyrosine kinase which is commonly overexpressed in tumors. [43,47,49]
Regulates both apoptosis and proliferation
Inhibited by chemotherapeutic drugs (tamoxifen and adrenergic antagonists) [50,51]

EAG expression and activity have been demon-
strated not only in tumor cell lines but also in several
primary human cancers; comparative studies in the
corresponding normal tissues have stressed the
potential clinical relevance of EAG.
Erg channels were found to be more frequently
expressed in human endometrial cancer as compared
to non-cancerous endometrium, while it was not
found in endometrial hyperplasia [37]; the authors
suggested h-erg channels as potential tools discrimi-
nating endometrial cancer from simple hyperplasia.
Studies of erg in leukemias and normal blood cells by
two different groups, led to the conclusion that erg is
constitutively activated in the neoplastic cells while
turned-off in normal cells [33,34], suggesting it as a
novel molecular marker for human neoplastic hema-
topoietic cells. Human lactotroph cells from prolacti-
noma tissue have also been reported to express erg
channels, its activity was suggested to participate in
the control of prolactin secretion, in accordance to its
role in normal rat lactotrophs [38].
Colorectal cancer, one of the leading causes of
cancer death, has also been subject of study for erg
expression. Erg transcripts and protein were found to
be expressed in a high percentage of primary human
colorectal cancers, with the highest incidence occur-
ring in metastatic cancers [36]. However, when
looking for erg in normal colonic mucosa or in
adenomas, no expression was found. Erg channels
were then suggested as potential prognostic factors for
colorectal cancer. Investigations in human gliomas
have also been made [39] that suggest a differential
expression of erg and eag1 depending on the
malignancy grade and nature of tumor cells; such
expression seems to be inversely related to the
malignancy of the tumor. Because EAG channels
are expressed in normal brain, the precise relationship
between EAG expression and brain tumors remains to
be elucidated.
Finally, a recent report relates eag1 expression and
channel activity to cervical cancer [40], the leading
cause of women death in some developing countries.
The group reported eag1 mRNA expression in 100%
of the cervical cancer samples studied and only in
33% of the normal control samples. Interestingly, they
observed that in one of the patients submitted to
 J. Camacho / Cancer Letters 233 (2006) 1–9
hysterectomy without any previous evidence of
cervical malignancy (negative pap smears), post-
surgery pathological studies showed an unexpected
endocervical adenocarcinoma expressing eag1. This
case, although unique in their study, emphasizes the
potential significance of eag1 as a tumor marker. In
addition, despite all of their control cervical samples
came from patients with negative pap smears, they
also found eag1 expression in some of such biopsies.
Quite interesting, diagnosis of one of those samples
was correlated to human papilloma virus infection, the
most important etiological factor for cervical cancer;
other control sample presented atypical adenomatous
hyperplasia of the endometrium, a predisposing
condition of endometrial cancer and in other control
eag-positive case, hystopathological studies reported
a paratubaric serous cystadenoma, a benign epithelial
ovarian tumor. A plausible scenario is that the
increase of eag1 expression in normal cervix could
be an early sign of tumor development. In addition,
they found channel expression and activity in cervical
cancer cells. The authors suggest that eag1 might be
not only a molecular marker and a potential
membrane therapeutic target for cervical cancer but
probably also an early indicator of the disease.
In addition to the expression and channel activity
studies, modulation and pharmacological experiments
have provided important clues for the potential
therapeutic use of EAG in cancer treatment and are
described below.
3.3. EAG modulation and cancer
Cell-cycle regulation of proteins, signal transduc-
tion pathways, extracellular matrix components,
tumor suppressor genes and hypoxia play important
roles in tumor development and have been key
elements when designing anticancer therapies. Modu-
lation of EAG channels by such elements has been
studied in different cancer cells.
Induction of human neuroblastoma cells differen-
tiation by retinoic acid reduces eag1 current in more
than 95% and also changes the voltage-dependent
properties of erg channels [32]; in other differen-
tiation study, it was shown that in a human leukemic
cell line undergoing differentiation after adhesion to
fibronectin, erg current was early activated in
adhering cells [48]. In comparison to unsynchronized
5
MCF-7 cells, from human breast cancer, eag1 mRNA
expression is significantly increased in cells in the G1
phase of the cell cycle but then lowered in the S phase
[41]. Very fine regulation of EAG channels during cell
cycle was reported in tumor cell lines from different
histogenesis [42]; erg isoforms are differentially
regulated during cell cycle; one of these isoforms
lacks the PAS domain, an oxygen sensor. Actually,
erg channels are modulated by hypoxia, a key element
in tumor progression. Neuroblastoma cells exposed to
hypoxia undergo profound changes in its gating
properties [43].
Eag1 has also been somehow related to hypoxia.
The von Hippel-Lindau (VHL) tumor suppressor
gene, linked to the development of sporadic heman-
gioblastomas and clear-cell renal carcinomas, plays a
central role in the oxygen sensing pathway because of
its close interaction with the hypoxia-inducible factor
[HIF, reviewed in Ref. [44]]. In the absence of the
VHL protein, HIF becomes stabilized and is free to
induce the expression of cancer related genes such as
those regulating angiogenesis, cell growth or cell
survival. Expression of the VHL protein in human
neuroblastoma cells switched-off drastically eag1
mediated currents; accordingly, VHL inhibition
increased eag1 channel activity in comparison to
control cells [45].
Other modulation studies have also provided very
interesting information. Intracellular calcium at nano-
molar concentrations inhibits eag1 currents through
calmodulin binding to the eag1 C-terminus [46], the
binding is calcium dependent with an apparent KD of
480 nM. Because of calcium has a regulatory role
during cell cycle, the authors proposed to elucidate
whether this calcium regulation of eag1 is an
important link between these channels and tumor
progression. Src tyrosine kinases are overexpressed in
a variety of human tumors and are an integral part of
tumor signaling pathways associated with migration,
proliferation, adhesion and angiogenesis; co-immu-
noprecipitation studies suggest that rat erg channels
appears to exist in a signaling complex with Src
tyrosine kinase. Erg channel activity was reduced by
the Src-selective inhibitory peptide and the current
was increased by the Src-activating peptide [47].
Studies of protein associations revealed that epsin
binds to eag1 channels modulating its gating proper-
ties [54]. Epsins are proteins that function at
6 J. Camacho / Cancer Letters 233 (2006) 1–9
the plasma membrane in the internalization steps of
endocytosis [reviewed in Ref. [55]], thus epsin
binding to eag1 represents a potential link between
cell growth and eag1 channels that deserves further
investigations. Finally, it has been shown that human
erg channels might be regulators of both apoptosis
and proliferation. On one hand, erg channel activity
markedly promotes H2O2-induced apoptosis of var-
ious tumor cells, blockade of erg inhibited such
induced apoptosis. On the other hand, erg expression
facilitated the tumor cell proliferation caused by
tumor necrosis factor [49].
3.4. EAG pharmacology and cancer drugs
Specific blockers for erg channels have been
extensively used, mainly because of their pivotal
role in the LQT2 syndrome [reviewed in Refs.
[15,20]] but the specific block has been also shown
to inhibit cell proliferation in tumor cell lines from
different histogenesis [34]. Interestingly, chemother-
apeutic drugs like tamoxifen (widely used in breast
cancer treatment) and a1-adrenoceptors antagonists
(used in the treatment of benign prostatic hyperplasia)
also inhibit erg channel activity [50,51]. Unfortu-
nately, there are no specific blockers for eag1,
however, as in the case for erg, some non-specific
blockers have been shown to inhibit eag1 and
decrease cell proliferation in tumor cell lines.
Imipramine, a tryciclic antidepressant and the anti-
histamine astemizole inhibit eag1 [52,53]; imi-
pramine impairs cell proliferation in human
melanoma cell lines expressing eag1 [52].
Non-specific EAG channel inhibition by che-
motherapeutic drugs offers alternative mechanisms
explaining the anti-proliferative effect of some
chemotherapeutic compounds and provide insights
for the design of new anti-cancer drugs.
4. Hypothetical scenarios on oncogenicity
mechanisms
Potassium channels activity has been related to cell
cycle progression, oncogenesis and proliferation, and
although the precise mechanism involved has not
been elucidated, several hypothesis have been
suggested [reviewed in Refs. [7–9,56]]. Potassium
efflux through potassium channels induces hyperpol-
arization and changes in cell volume. Hyperpolariz-
ation increases the driving force for calcium ions—
which might interact with cell cycle proteins—and on
the other hand, cell size has been closely related to
cell proliferation; however, it has been confirmed in
numerous studies that cancer cells are more depolar-
ized than non-tumor cells. Clearly, additional clues
must be found and alternative mechanisms uncovered.
Probably, particular characteristics like special struc-
tural features, protein–protein interactions and modu-
lation of potassium channels by cell cycle—or cancer-
related factors might provide such clues; EAG
channels possess some of these particular properties,
hence more hypothetical scenarios might be suggested
in addition to the described above (Fig. 1).
EAG interacts with and is modulated by proteins
related to cell cycle and/or cancer like epsin, Src
tyrosine kinase, calmodulin and integrins. In addition,
modulation of EAG also includes important elements
involved in tumor progression like hypoxia, tumor
suppressor genes (also related to hypoxic conditions),
cytoskeletal elements and differentiation-inducing
factors. An intriguing question remains: what happens
in the opposite direction? Inhibition of EAG (either
expression or channel activity) decreases cell pro-
liferation. How does changes in channel activity
modify the interaction of EAG with the cell cycle—or
cancer-related proteins? Is EAG channel activity
necessary to maintain such interactions? Does EAG
channel activity modify the intrinsic activity of its
binding proteins, controlling indirectly tumor pro-
gression? How is such interaction modulated for
example, by hypoxic conditions? Ubiquitous EAG
channels expression in tumors might be compatible
with the idea of considering EAG as modulators of
cell cycle—and cancer-related proteins. Actually it
has been recently demonstrated that human erg
channels and integrins co-precipitate in tumor cells
and it was suggested that the protein and its channel
activity can modulate integrin downstream signaling
[57]. Another unsolved question is how EAG channels
expression is induced. Is HPV infection related to
EAG expression? or, do other viruses, oncogenes or
hormones induce EAG expression? Addressing some
of these issues will help for a better understanding of
the relationship between EAG and cancer. We are
already trying to solve some of these questions.
 J. Camacho / Cancer Letters 233 (2006) 1–9 7

Mitogenic signals Oncogenes Anti-apoptotic

(hormones, growth factors) signals

Chemical E AG exp re ss ion?

Human papilloma or
carcinogens other viruses

H y p o x i a , d if f e re n t ia ti o n
an d drug s
eag1 erg
Apoptosis
Membrane potential
? changes. K+ efflux ?
?
?
Ca2+ ? Cell volume
influx changes
Epsin ? ? Src tyrosine
Calmodulin kinase
Cytoskeleton Integrins
VHL protein Tumor Necrosis
(HIF-related) Proliferation Factor
Metastasis
Apoptosis
prevention

Fig. 1. Hypothetical scenarios on the mechanisms of EAG oncogenicity: EAG channels as modulators of cell cycle and cancer-related proteins?
It has been suggested that potassium channels activity would relate to cell proliferation by increasing calcium influx and modifying cell volume.
However, since EAG channels are modulated by several cell cycle and cancer-related proteins as well as hypoxic conditions and inhibited by
some anti-cancer drugs, alternative explanations would arise if at least some of such elements are in turn modulated by the EAG protein and/or
channel activity. In such hypothetical model, EAG channels would be indirect but more general inducers of proliferation.

5. Conclusions tissues—among many other studies needed—will

help to elucidate how EAG channels become turned-
Expression and channel activity studies have on and their precise participation in regulating or
highlighted the tight association between EAG and promoting proliferation in health and disease.
cancer; furthermore, modulation and pharmacological
experiments have provided important clues for the
potential therapeutic use of EAG in cancer treatment.
Because of its restricted distribution in normal Acknowledgements
tissues and its more ubiquitous distribution in cancer
The author is deeply grateful to Walter Stühmer
cells, EAG channels represent promising tools for the
and Luis Pardo (MPI, Göttingen Germany) for
development of improved diagnose cancer methods.
supporting significantly his scientific career. The
In addition, since channel inhibition impairs cell
author’s laboratory has received financial support by
proliferation in tumor cell lines, EAG channels also
the Consejo Nacional de Ciencia y Tecnologı́a.
represent interesting targets for the directed design of
anti-cancer therapies.
The study of the relationship between molecularly
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