Blocking The Pathway
1st Oct 13:
Blocking Cancer Cell Pathway Shown to Reduce Spread of Mesothelioma Cells September 30, 2013 by Steven Kazan Leave a Comment Coping with mesothelioma forces you to learn a lot of scientific medical information you never would have predicted you’d want to know about. But mesothelioma is what’s on your plate now and medical knowledge is what you need. And we are here to help provide it to you when we see something out there we think you ought to know about.
Right now, we think you need to know about hedgehogs. Really. And if you think we mean those cute spiky animals seen mostly in children’s story books, think again. We’re talking about science. Specifically a cell development phase interestingly called “the hedgehog signaling pathway.” You need to know about it because scientists now think that this pathway may lead the way to cancer cell development and they are looking at ways to block this pathway in the hopes of preventing the formation of cancer cells. So this hedgehog pathway might lead the way to successfully treating hard to treat cancers like mesothelioma.
In the 1970s, scientists struggled to understand exactly how an insect egg or a human embryo knew how to grow cells that would turn into complex segmented body parts like legs and toes. Using fruit fly genes, scientists in 1980 discovered a genetic sequence that ensures that developing tissue obtain their correct size, location and cellular content. Because their experiments resulted in fruit fly larvae that had a spiky appearance, they named the genetic sequence “the hedgehog signaling pathway.”
As you can imagine, this hedgehog signaling pathway is very important during the embryo’s development. But then it is supposed to go into hibernation. Except for tissue maintenance and repair, it is supposed to be dormant in adults. Its reactivation now has been linked to the development of several types of cancer, including mesothelioma. Blocking it may offer a potential therapeutic target for new cancer treatment options.
A new study from the University of California San Francisco, using tissue samples from 46 volunteers with malignant pleural mesothelioma, found that aberrant activation of the hedgehog signaling pathway activates the “Glioma-associated oncogene (Gli) family of transcription factors.”[1] Oncogenes make the cancer cells that spur mesothelioma tumor growth. Basically, it’s like waking up the evil zombies and then they run amok. The study, published earlier this year, further found that specifically blocking the Gli activity was better at reducing the spread of mesothelioma cells than just blocking the overall hedgehog signaling pathway.
“Our results strongly suggest that targeting Gli factors holds strong potential for clinically effective treatment options for MPM patients in the near future,” the researchers conclude.
The researchers kindly acknowledge the Kazan law firm’s charitable foundation for its contribution to this project along with the National Cancer Institute and other funding sources.
Study Represents First-in-Asia Use of Lead FAK Inhibitor to Target Cancer Stem Cells
CAMBRIDGE, Mass.--(BUSINESS WIRE)--September 24, 2013--
Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today announced the initiation of a Phase 1 trial of defactinib (VS-6063), a potent inhibitor of focal adhesion kinase (FAK), in Japanese patients with advanced solid tumors. FAK is a pathway critical for the growth and survival of cancer stem cells and the study marks the launch of Verastem's development efforts in Japan.
The Phase 1 open-label, dose-escalation study, which will be conducted at Kinki University in Osaka, is designed to assess the safety, pharmacokinetics and pharmacodynamics of single agent defactinib. The study will enroll 12-18 patients. Pending a successful outcome to the Phase 1 study, Verastem may add additional clinical sites in Japan to the recently initiated COMMAND trial, a global registration-directed study of defactinib in patients with malignant pleural mesothelioma, and may pursue additional development efforts in Japan.
"Initiation of this trial is another important clinical milestone for Verastem and for defactinib, a drug candidate which is now being studied at sites in 12 countries over five continents," said Dr. Joanna Horobin, Verastem Chief Medical Officer. "In the US Phase 1 study, defactinib demonstrated good tolerability, as well as early signs of activity. With this study we hope to take the first steps toward a path to registration in Japan in parallel to our efforts in Europe and the US."
"The simultaneous Japanese development of defactinib with the ongoing efforts in the United States and Europe is highly exciting," said Professor Kazuhiko Nakagawa, M.D., Ph.D., Director, Department of Medical Oncology, Kinki University Faculty of Medicine and Coordinating Investigator for defactinib development in Japan. "At Kinki University, we are dedicated to accelerating the development of novel compounds such as defactinib that have the potential to make a significant difference in the treatment of cancer for our patients in Japan."
Historically, the initiation of development in Japan for most drugs has been delayed in comparison to efforts in the US and EU. Verastem is pursuing a rapid expansion of the geographical development of defactinib in an attempt to rapidly make defactinib available for patients worldwide.
"We are pleased to take part in this novel Phase 1 trial of defactinib that targets cancer stem cells," said Toshio Shimizu, M.D., Principal Investigator of the Phase 1 study. "Led by scientific breakthroughs from Professor Robert Weinberg on the role of focal adhesion kinase in cancer stem cells, Verastem is taking a new approach to the treatment of cancer in an attempt to address the underlying cause of disease progression and tumor recurrence."
"With a dramatic rise in the incidence of mesothelioma in Japan, it is imperative that new treatments with the potential to address this deadly disease are developed in parallel with other major markets," said Christoph Westphal, M.D., Ph.D., Verastem Executive Chairman. "Initiation of this study in Japan serves to underscore our passion for carrying out Verastem's mission, which is to deliver new medicines that will make a meaningful difference in the lives of cancer patients around the world."
About Defactinib
Defactinib (VS-6063) is an oral 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 the FAK pathway is critical for the growth and survival of cancer stem cells. Defactinib is currently being studied in the registration-directed COMMAND trial in mesothelioma, a Phase 1/1b study in ovarian cancer and a Phase 1 study in Japan. A Phase 2 trial in KRAS-mutated Non-Small Cell Lung Cancer is expected to begin in the third quarter of 2013. Defactinib has been granted orphan drug designation in the U.S. and E.U. for use in mesothelioma.
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.
Forward-looking statements:
This press release includes forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development of the Company's compounds, including VS-6063, or defactinib, and the Company's FAK and diagnostic programs generally, the timeline for clinical development and regulatory approval of the Company's compounds, the expected timing for the reporting of data from ongoing trials, the structure of the Company's planned or pending clinical trials and estimates of the Company's ability to fund operations. 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 compounds and preliminary data from clinical trials may not be predictive of the results or success of later clinical trials, 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 its compounds, including defactinib, that the development of the Company's compounds will take longer or cost more than planned, and that the Company's compounds 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 December 31, 2012 and in any subsequent SEC filings. The forward-looking statements contained in this presentation reflect the Company's current views with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements.
CONTACT: Verastem, Inc.
Brian Sullivan, 617-252-9314
[email protected]
SOURCE: Verastem, Inc. Copyright Business Wire 2013
The Wall Street Journal news department was not involved in the creation of this content.
Blocking Cancer Cell Pathway Shown to Reduce Spread of Mesothelioma Cells September 30, 2013 by Steven Kazan Leave a Comment Coping with mesothelioma forces you to learn a lot of scientific medical information you never would have predicted you’d want to know about. But mesothelioma is what’s on your plate now and medical knowledge is what you need. And we are here to help provide it to you when we see something out there we think you ought to know about.
Right now, we think you need to know about hedgehogs. Really. And if you think we mean those cute spiky animals seen mostly in children’s story books, think again. We’re talking about science. Specifically a cell development phase interestingly called “the hedgehog signaling pathway.” You need to know about it because scientists now think that this pathway may lead the way to cancer cell development and they are looking at ways to block this pathway in the hopes of preventing the formation of cancer cells. So this hedgehog pathway might lead the way to successfully treating hard to treat cancers like mesothelioma.
In the 1970s, scientists struggled to understand exactly how an insect egg or a human embryo knew how to grow cells that would turn into complex segmented body parts like legs and toes. Using fruit fly genes, scientists in 1980 discovered a genetic sequence that ensures that developing tissue obtain their correct size, location and cellular content. Because their experiments resulted in fruit fly larvae that had a spiky appearance, they named the genetic sequence “the hedgehog signaling pathway.”
As you can imagine, this hedgehog signaling pathway is very important during the embryo’s development. But then it is supposed to go into hibernation. Except for tissue maintenance and repair, it is supposed to be dormant in adults. Its reactivation now has been linked to the development of several types of cancer, including mesothelioma. Blocking it may offer a potential therapeutic target for new cancer treatment options.
A new study from the University of California San Francisco, using tissue samples from 46 volunteers with malignant pleural mesothelioma, found that aberrant activation of the hedgehog signaling pathway activates the “Glioma-associated oncogene (Gli) family of transcription factors.”[1] Oncogenes make the cancer cells that spur mesothelioma tumor growth. Basically, it’s like waking up the evil zombies and then they run amok. The study, published earlier this year, further found that specifically blocking the Gli activity was better at reducing the spread of mesothelioma cells than just blocking the overall hedgehog signaling pathway.
“Our results strongly suggest that targeting Gli factors holds strong potential for clinically effective treatment options for MPM patients in the near future,” the researchers conclude.
The researchers kindly acknowledge the Kazan law firm’s charitable foundation for its contribution to this project along with the National Cancer Institute and other funding sources.
Study Represents First-in-Asia Use of Lead FAK Inhibitor to Target Cancer Stem Cells
CAMBRIDGE, Mass.--(BUSINESS WIRE)--September 24, 2013--
Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, today announced the initiation of a Phase 1 trial of defactinib (VS-6063), a potent inhibitor of focal adhesion kinase (FAK), in Japanese patients with advanced solid tumors. FAK is a pathway critical for the growth and survival of cancer stem cells and the study marks the launch of Verastem's development efforts in Japan.
The Phase 1 open-label, dose-escalation study, which will be conducted at Kinki University in Osaka, is designed to assess the safety, pharmacokinetics and pharmacodynamics of single agent defactinib. The study will enroll 12-18 patients. Pending a successful outcome to the Phase 1 study, Verastem may add additional clinical sites in Japan to the recently initiated COMMAND trial, a global registration-directed study of defactinib in patients with malignant pleural mesothelioma, and may pursue additional development efforts in Japan.
"Initiation of this trial is another important clinical milestone for Verastem and for defactinib, a drug candidate which is now being studied at sites in 12 countries over five continents," said Dr. Joanna Horobin, Verastem Chief Medical Officer. "In the US Phase 1 study, defactinib demonstrated good tolerability, as well as early signs of activity. With this study we hope to take the first steps toward a path to registration in Japan in parallel to our efforts in Europe and the US."
"The simultaneous Japanese development of defactinib with the ongoing efforts in the United States and Europe is highly exciting," said Professor Kazuhiko Nakagawa, M.D., Ph.D., Director, Department of Medical Oncology, Kinki University Faculty of Medicine and Coordinating Investigator for defactinib development in Japan. "At Kinki University, we are dedicated to accelerating the development of novel compounds such as defactinib that have the potential to make a significant difference in the treatment of cancer for our patients in Japan."
Historically, the initiation of development in Japan for most drugs has been delayed in comparison to efforts in the US and EU. Verastem is pursuing a rapid expansion of the geographical development of defactinib in an attempt to rapidly make defactinib available for patients worldwide.
"We are pleased to take part in this novel Phase 1 trial of defactinib that targets cancer stem cells," said Toshio Shimizu, M.D., Principal Investigator of the Phase 1 study. "Led by scientific breakthroughs from Professor Robert Weinberg on the role of focal adhesion kinase in cancer stem cells, Verastem is taking a new approach to the treatment of cancer in an attempt to address the underlying cause of disease progression and tumor recurrence."
"With a dramatic rise in the incidence of mesothelioma in Japan, it is imperative that new treatments with the potential to address this deadly disease are developed in parallel with other major markets," said Christoph Westphal, M.D., Ph.D., Verastem Executive Chairman. "Initiation of this study in Japan serves to underscore our passion for carrying out Verastem's mission, which is to deliver new medicines that will make a meaningful difference in the lives of cancer patients around the world."
About Defactinib
Defactinib (VS-6063) is an oral 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 the FAK pathway is critical for the growth and survival of cancer stem cells. Defactinib is currently being studied in the registration-directed COMMAND trial in mesothelioma, a Phase 1/1b study in ovarian cancer and a Phase 1 study in Japan. A Phase 2 trial in KRAS-mutated Non-Small Cell Lung Cancer is expected to begin in the third quarter of 2013. Defactinib has been granted orphan drug designation in the U.S. and E.U. for use in mesothelioma.
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.
Forward-looking statements:
This press release includes forward-looking statements about the Company's strategy, future plans and prospects, including statements regarding the development of the Company's compounds, including VS-6063, or defactinib, and the Company's FAK and diagnostic programs generally, the timeline for clinical development and regulatory approval of the Company's compounds, the expected timing for the reporting of data from ongoing trials, the structure of the Company's planned or pending clinical trials and estimates of the Company's ability to fund operations. 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 compounds and preliminary data from clinical trials may not be predictive of the results or success of later clinical trials, 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 its compounds, including defactinib, that the development of the Company's compounds will take longer or cost more than planned, and that the Company's compounds 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 December 31, 2012 and in any subsequent SEC filings. The forward-looking statements contained in this presentation reflect the Company's current views with respect to future events, and the Company does not undertake and specifically disclaims any obligation to update any forward-looking statements.
CONTACT: Verastem, Inc.
Brian Sullivan, 617-252-9314
[email protected]
SOURCE: Verastem, Inc. Copyright Business Wire 2013
The Wall Street Journal news department was not involved in the creation of this content.
