Verastem and Cancer STEM cells with FAK inhibitors

Dr. Weeks’ Comment: Now that drug companies are seeing their way to selling expensive agents to fight cancer STEM cells, we will be told that cancer STEM cells, after all, are the target. Just remember that “FAK  inhibitors”  are fancy words for  …..  anti-inflammatory agents. Get your SOUL.

“…The clinical relevance of cancer stem cells (CSCs) has perhaps been best documented in breast cancer…”

“… Neoadjuvant chemotherapy has been shown to lead to an increase in CSCs in locally advanced breast cancer. In addition, the presence of CSCs in residual axillary disease is associated with a significantly worse prognosis following neoadjuvant chemotherapy and surgery…”

BOSTON  December 11, 2014– (BUSINESS WIRE)–Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today announced a poster presentation at the 2014 San Antonio Breast Cancer Symposium (SABCS) taking place December 9 – 13, 2014.

“The clinical relevance of cancer stem cells (CSCs) has perhaps been best documented in breast cancer”

“The clinical relevance of cancer stem cells (CSCs) has perhaps been best documented in breast cancer,” said Jonathan Pachter, Ph.D., Verastem Head of Research. “Our new data demonstrate the functional relevance of the effective knock down of cancer stem cells by our FAK inhibitors, VS-6063 and VS-4718, in preclinical models of triple negative breast cancer. As single agents in these models, both FAK inhibitors effectively extended anti-tumor activity after cessation of chemotherapy, and induced regression of metastatic lesions. This work builds upon the existing body of preclinical proof-of-concept data supporting the functional relevance of cancer stem cells and supports the planned clinical development of a FAK inhibitor for breast cancer.”

Verastem is presenting these preclinical data in support of its VS-6063 and VS-4718 development programs targeting cancer stem cells through inhibition of the focal adhesion kinase (FAK) signaling pathway. Research on the FAK signaling pathway has revealed critical roles for each in CSC survival and disease progression. 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.

A summary of the data presented at the conference is below:

Title: VS-6063 (defactinib) and VS-4718 Reduce Cancer Stem Cells in Models of Breast Cancer: Implications for Clinical Trials in the Neoadjuvant Setting

Summary: In breast cancer, CSCs can be identified by Aldehyde Dehydrogenase 1 (ALDH) or CD44-high/CD24-low expression. Neoadjuvant chemotherapy has been shown to lead to an increase in CSCs in locally advanced breast cancer. In addition, the presence of CSCs in residual axillary disease is associated with a significantly worse prognosis following neoadjuvant chemotherapy and surgery. Currently, there are no approved therapies that effectively target and kill CSCs. VS-6063 and VS-4718 are orally bioavailable small molecules that kill cancer stem cells through the inhibition of FAK, and both compounds have demonstrated preferential targeting of CSCs in preclinical models. In this study, the effects of VS-6063 and VS-4718 were evaluated in multiple breast cancer models.

The research results demonstrated that CSCs are readily detectable in primary breast cancers at surgery, and VS-6063 and VS-4718 diminish the CSC subpopulation in vitro, ex vivo and in xenograft models, as measured by a number of functional and biomarker assays. This critical subpopulation of CSCs is also detectable in residual tumor following neoadjuvant therapy. These results provide scientific rationale for the clinical development of VS-6063 in combination with chemotherapy for the neoadjuvant treatment of TNBC and support the clinical investigation of CSC-targeted agents such as VS-6063 or VS-4718 in the neoadjuvant setting to potentially delay time to relapse and improve patient outcomes.

A copy of the poster presentation is available at http://bit.ly/R3M6wc.

 

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 Robert Weinberg, Ph.D., scientific cofounder and chair of Verastem’s Scientific Advisory Board, and Verastem has demonstrated that FAK activity is critical for the growth and survival of cancer stem cells. VS-6063 is currently being studied in the registration-directed COMMAND trial in mesothelioma (www.COMMANDmeso.com), a “Window of Opportunity” study in patients with mesothelioma prior to surgery, a Phase 1/1b study in combination with paclitaxel in patients with ovarian cancer, and a trial in patients with Kras-mutated non-small cell lung cancer. VS-6063 has been granted orphan drug designation in the U.S. and EU for use in mesothelioma.

 

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 Verastem, Inc.

Verastem, Inc. (NASDAQ:VSTM) is discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. Verastem is developing small molecule inhibitors of signaling pathways that are critical to cancer stem cell survival and proliferation: FAK, PI3K/mTOR and Wnt.

Verastem Presents Data at the 2014 San Antonio Breast Cancer Symposium

December 11, 2014

 

BOSTON– (BUSINESS WIRE)–Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today announced a poster presentation at the 2014 San Antonio Breast Cancer Symposium (SABCS) taking place December 9 – 13, 2014.

“The clinical relevance of cancer stem cells (CSCs) has perhaps been best documented in breast cancer”

“The clinical relevance of cancer stem cells (CSCs) has perhaps been best documented in breast cancer,” said Jonathan Pachter, Ph.D., Verastem Head of Research. “Our new data demonstrate the functional relevance of the effective knock down of cancer stem cells by our FAK inhibitors, VS-6063 and VS-4718, in preclinical models of triple negative breast cancer. As single agents in these models, both FAK inhibitors effectively extended anti-tumor activity after cessation of chemotherapy, and induced regression of metastatic lesions. This work builds upon the existing body of preclinical proof-of-concept data supporting the functional relevance of cancer stem cells and supports the planned clinical development of a FAK inhibitor for breast cancer.”

 

Verastem is presenting these preclinical data in support of its VS-6063 and VS-4718 development programs targeting cancer stem cells through inhibition of the focal adhesion kinase (FAK) signaling pathway. Research on the FAK signaling pathway has revealed critical roles for each in CSC survival and disease progression. 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.

 

A summary of the data presented at the conference is below:

Title: VS-6063 (defactinib) and VS-4718 Reduce Cancer Stem Cells in Models of Breast Cancer: Implications for Clinical Trials in the Neoadjuvant Setting

Summary: In breast cancer, CSCs can be identified by Aldehyde Dehydrogenase 1 (ALDH) or CD44-high/CD24-low expression. Neoadjuvant chemotherapy has been shown to lead to an increase in CSCs in locally advanced breast cancer. In addition, the presence of CSCs in residual axillary disease is associated with a significantly worse prognosis following neoadjuvant chemotherapy and surgery. Currently, there are no approved therapies that effectively target and kill CSCs. VS-6063 and VS-4718 are orally bioavailable small molecules that kill cancer stem cells through the inhibition of FAK, and both compounds have demonstrated preferential targeting of CSCs in preclinical models. In this study, the effects of VS-6063 and VS-4718 were evaluated in multiple breast cancer models.

The research results demonstrated that CSCs are readily detectable in primary breast cancers at surgery, and VS-6063 and VS-4718 diminish the CSC subpopulation in vitro, ex vivo and in xenograft models, as measured by a number of functional and biomarker assays. This critical subpopulation of CSCs is also detectable in residual tumor following neoadjuvant therapy. These results provide scientific rationale for the clinical development of VS-6063 in combination with chemotherapy for the neoadjuvant treatment of TNBC and support the clinical investigation of CSC-targeted agents such as VS-6063 or VS-4718 in the neoadjuvant setting to potentially delay time to relapse and improve patient outcomes.

A copy of the poster presentation is available at http://bit.ly/R3M6wc.

 

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 Robert Weinberg, Ph.D., scientific cofounder and chair of Verastem’s Scientific Advisory Board, and Verastem has demonstrated that FAK activity is critical for the growth and survival of cancer stem cells. VS-6063 is currently being studied in the registration-directed COMMAND trial in mesothelioma (www.COMMANDmeso.com), a “Window of Opportunity” study in patients with mesothelioma prior to surgery, a Phase 1/1b study in combination with paclitaxel in patients with ovarian cancer, and a trial in patients with Kras-mutated non-small cell lung cancer. VS-6063 has been granted orphan drug designation in the U.S. and EU for use in mesothelioma.

 

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 Verastem, Inc.

Verastem, Inc. (NASDAQ:VSTM) is discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells. Cancer stem cells are an underlying cause of tumor recurrence and metastasis. Verastem is developing small molecule inhibitors of signaling pathways that are critical to cancer stem cell survival and proliferation: FAK, PI3K/mTOR and Wnt. For more information, please visit www.verastem.com.

 

 

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Dr. Weeks’ Comment: Now that drug companies are seeing their way to selling expensive agents to fight cancer STEM cells, we will be told that cancer STEM cells, after all, are the target. Just remember that “FAK  inhibitors”  are fancy words for  …..  anti-inflammatory agents. Get your SOUL. “…The clinical relevance of cancer stem cells (CSCs) has…
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