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Verastem Announces Publication of Scientific Data for VS-5584 in Cancer Research
The paper discusses results from preclinical research evaluating VS-5584, a highly potent, selective small molecule inhibitor of mTORC1/2 and Class I PI3K kinases, which preferentially targets cancer stem cells (CSCs) in vitro and in vivo. CSCs represent a subpopulation of cancer cells that have tumor-initiating capability, are particularly resistant to chemotherapy and can mediate tumor recurrence both locally and at metastatic sites.
“In this study, we show clear evidence that the biological inhibition of
PI3K alpha, beta and mTOR together, in contrast to inhibition of any one
member of the pathway alone, is necessary for the killing of cancer stem
cells across different carcinoma types, including breast, ovarian and
small cell lung cancer,” said
The study results demonstrated that VS-5584 is up to 30-fold more potent in inhibiting the proliferation and survival of CSCs compared to non-CSCs in solid tumor cell populations. VS-5584 preferentially diminished CSC levels in multiple mouse xenograft models of human cancer. Similarly, VS-5584 treatment ex vivo preferentially reduced CSCs in surgically resected breast and ovarian patient tumors. In contrast, chemotherapeutics such as paclitaxel, cisplatin and etoposide effectively targeted bulk tumor cells, but enriched CSCs. Mechanistic investigations revealed that knock down of PI3Kα, PI3Kβ or mTOR alone was insufficient to decrease CSCs, while knock down of PI3Kα, PI3Kβ and mTOR together effectively reduced CSCs mimicking the effect of VS-5584. Consistent with CSC ablation, VS-5584 delayed tumor regrowth following chemotherapy in xenograft models of small cell lung cancer. These data help to elucidate the mechanism of VS-5584 targeting CSCs and provide a strong rationale for the clinical development of VS-5584 in combination with chemotherapeutic agents targeting bulk tumor cells to achieve more durable clinical responses in cancer patients.
The full publication can be accessed online at http://bit.ly/1FR8DEB
About VS-5584
VS-5584 is an orally available compound that has demonstrated potent and
highly selective activity against class 1 PI3K enzymes and dual
inhibitory actions against mTORC1 and mTORC2. In preclinical studies,
VS-5584 has been shown to reduce the percentage of cancer stem cells and
induce tumor regression in chemotherapy-resistant models.
About
Forward-looking statements:
This press release includes forward-looking statements about the
Company’s strategy, future plans and prospects, including statements
regarding the activity of the Company’s product candidate VS-5584 and
the Company’s PI3K/mTOR program generally and the proposed clinical
development of VS-5584. The words “anticipate,” “appear,” “believe,”
“estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,”
“target,” “potential,” “will,” “would,” “could,” “should,” “continue,”
and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain these
identifying words. Each forward-looking statement is subject to risks
and uncertainties that could cause actual results to differ materially
from those expressed or implied in such statement. Applicable risks and
uncertainties include the risks that the preclinical testing of VS-5584
and preliminary or interim data from clinical trials may not be
predictive of the results or success of ongoing or later clinical trials
with VS-5584, that data may not be available when we expect it to be,
that the Company will be unable to successfully complete the clinical
development of VS-5584, and that VS-5584 will not receive regulatory
approval or become a commercially successful product. Other risks and
uncertainties include those identified under the heading “Risk Factors”
in the Company’s Annual Report on Form 10-K for the year ended
Source:
Verastem, Inc.
Brian Sullivan, 781-292-4214
bsullivan@verastem.com
