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Verastem Presents Encouraging Scientific Data on the Preferential Targeting of Cancer Stem Cells at the 2015 American Association of Cancer Research Annual Meeting
“The scientific research presented by both
Details for the data presentations at AACR are as follows:
Oral Presentation
Title: FAK inhibitors VS-6063 and VS-4718 target cancer stem
cells: Implications for TNBC sequential and combination therapies
Date
and time:
Location:
Abstract number: 974
Session: Session
Title: Cancer Stem Cells 1; Session Category: Tumor Biology; Session
Type: Minisymposium
Summary: Neoadjuvant chemotherapy has
been shown to lead to an increase in markers of cancer stem cells (CSCs)
in primary breast cancer. The presence of the ALDH cancer stem cell
marker in residual cancer tissue in lymph nodes at surgery after
neoadjuvant chemotherapy has been associated with a significantly worse
prognosis following primary treatment. It is also evident that stem-like
features of tumor cells are present in metastatic breast cancer
indicating that targeting of CSCs may be valuable in metastatic disease.
Verastem’s CSC inhibitors, VS-6063 and VS-4718, diminished CSCs in
vitro, ex vivo and in xenograft models in contrast to
paclitaxel or cisplatin treatment which enriched CSCs. Consistent with
the notion that CSCs are responsible for cancer relapse after
chemotherapy, VS-6063 and VS-4718 substantially delayed tumor growth
following cessation of paclitaxel or cisplatin treatment in models of
triple negative breast cancer. Additionally, both VS-6063 and VS-4718
inhibited metastatic outgrowth and/or induced regression of metastases
after primary tumor resection, whereas metastases progressed in all
animals in the control group. These results support the clinical
investigation of the CSC-targeting agents VS-6063 and VS-4718 in certain
breast cancer settings to potentially delay time to relapse and improve
the treatment outcome.
A copy of the oral presentation is available at http://bit.ly/12otlcV
Poster Presentations
Title: FAK and PI3K/mTOR inhibitors target cancer stem cells:
Implications for SCLC treatment strategies
Date and time:
Location:
Section 19; Poster Board 24
Abstract Number: 1525
Session:
Session Title: Solid Tumor Stem Cells; Session Category: Tumor Biology
Summary:
In most patients with small cell lung cancer (SCLC), tumors
initially respond to first line chemotherapy, but subsequently
experience rapid recurrence. In previously reported research,
preclinical models of other cancers demonstrated that CSC populations
are increased following chemotherapy, and that inhibitors of FAK and
PI3K/mTOR have been shown to preferentially target CSCs. FAK and
PI3K/mTOR inhibitors may be particularly valuable in a SCLC setting,
where CSCs may be strong mediators of recurrence. In this study, the
antitumor activity of FAK and PI3K/mTOR inhibitors (VS-4718 and VS-5584,
respectively) were investigated in SCLC xenograft models in vivo.
In the preclinical models studied, the standard-of-care agents, cisplatin and etoposide, enriched the proportion of CSCs. In direct contrast, both VS‐5584 and VS‐4718 reduced SCLC CSCs in vivo when combined with chemotherapy. VS‐5584 and VS‐4718 also delayed tumor regrowth after treatment with these cytotoxic agents in SCLC xenograft models of switch maintenance therapy. The preferential targeting of CSCs in preclinical SCLC models provides an important rationale for clinical development of VS‐5584 and VS‐4718 in combination with chemotherapy to potentially lengthen the time to relapse and improve the treatment outcome for patients with SCLC.
A copy of the poster presentation is available at http://bit.ly/12otlcV
Title: FAK inhibitor VS-6063 (defactinib) targets mesothelioma
cancer stem cells, which are enriched by standard of care chemotherapy
Date
and time:
Location:
Section 21; Poster Board 23
Abstract Number: 4236
Session:
Session Title: Therapeutics Targeting Cancer Stem Cells; Session
Category: Tumor Biology
Summary: Malignant pleural
mesothelioma (MPM) is an aggressive tumor in the lining of the lung and
median overall survival with standard of care chemotherapy is only 12
months. This poor prognosis may be attributable at least in part to CSCs
which are resistant to chemotherapy and can mediate cancer recurrence
and progression. FAK has been shown to play an essential role in the
survival, self-renewal and tumor-initiating capability of CSCs.
In the preclinical models and patient biopsies studied, two standard-of-care agents, pemetrexed and platinum, enrich the proportion of CSCs. In direct contrast, the FAK inhibitor, VS-6063, markedly reduced CSCs in models of mesothelioma. In addition, in tumors that are low in the biomarker merlin, marked bulk tumor reduction was observed. In a switch maintenance model, VS-6063 treatment also delayed tumor regrowth following cisplatin plus pemetrexed treatment in vivo. These data provide strong rationale for the current clinical testing of VS-6063 in Verastem’s registration-directed COMMAND trial, evaluating VS-6063 in a maintenance setting to potentially prolong response to front line chemotherapy in patients with mesothelioma.
A copy of the poster presentation is available at http://bit.ly/12otlcV
Title: Targeting Focal Adhesion Kinase is a novel approach to
therapy of high-risk, Ikaros-mutant acute B-cell lymphoblastic leukemia
Date
and time:
Location:
Section 20; Poster Board 17
Abstract Number: 4202
Session:
Session Title: Mouse Models of Human Cancer 3; Session Category: Tumor
Biology
This research includes work on VS-4718 and was presented by collaborators. A copy of the poster presentation is available at http://bit.ly/12otlcV
About VS-6063
VS-6063 (defactinib) is an orally available
compound designed to target cancer stem cells through the potent
inhibition of focal adhesion kinase (FAK). Cancer stem cells are an
underlying cause of tumor resistance to chemotherapy, recurrence and
ultimate disease progression. Research by
About VS-4718
VS-4718 is an orally available compound
designed to target cancer stem cells through the potent inhibition of
focal adhesion kinase (FAK). VS-4718 is currently being studied in a
Phase 1 dose escalation study in patients with advanced cancers.
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 development and
activity of the Company’s product candidates, VS-6063, VS-4718 and
VS-5584, and the Company’s FAK and PI3K/mTOR, potential plans for
clinical development of the Company’s product candidates, and the
structure of the Company’s planned or pending clinical trials. 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 the Company’s product
candidates and preliminary or interim data from clinical trials may not
be predictive of the results or success of ongoing or later clinical
trials, that data may not be available when we expect it to be, that our
product candidates will cause unexpected safety events, that the Company
will be unable to successfully initiate or complete the clinical
development of its product candidates, that the development of the
Company’s product candidates will take longer or cost more than planned,
and that the Company’s product candidates will not receive regulatory
approval or become commercially successful products. 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