metastasis Archives - NFCR

metastasis

Attacking Metastatic Tumors in the Brain

Targeting HER3 could cripple metastatic cancers that have spread to the brain.

(Bethesda, MD, June 5, 2017) Rakesh Jain, PhD, Director of the Edwin L. Steele Laboratory for Tumor Biology at the Massachusetts General Hospital and supported by the National Foundation for Cancer Research, has discovered a novel mechanism behind the resistance to HER2- or PI3K-targeted therapies, and a treatment strategy that may overcome treatment resistance. This significant finding was reported in the latest issue of the journal Science Translational Medicine.

Rakesh Jain’s discovery could be very important for cancer patients whose cancers have spread to the brain.  About 20% to 25% of all breast cancers have an excess of a protein known as Human Epidermal Growth Factor Receptor 2 (HER2). HER2-positive (HER2+) breast cancer spreads more quickly than other types of breast cancer, and while several targeted therapies are now available to treat HER2+ breast cancer, putting this cancer into remission for years or longer in many patients, up to 50% of patients treated with these targeted therapies eventually develop brain metastases, which are inevitably fatal.

This research project directed by Dr. Jain may have unlocked a key as to why brain metastases are resistant to HER2+ targeted therapies, and have uncovered a potential treatment strategy to overcome this resistance.

Using tumor models and human cancer samples, the researchers found an overexpression of Human Epidermal Grown Factor Receptor 3 (HER3) in breast cancer-associated brain lesions, and that inhibiting HER3 could help overcome treatment resistance.  Dr. Jain’s team found that using drugs that target HER3 combined with those that target HER2 significantly slowed brain metastatic tumor growth and improved survival of the tumor models.  These results are the collaborative efforts between Rakesh Jain and Jeffrey A. Engelman, MD, PhD,  Global Head of Oncology at the Novartis Institutes for BioMedical Research (formerly with the MGH Cancer Center), an expert in targeted therapies and co-senior author of the publication.

Cancer therapies that target specific proteins often fail to reign in tumors that have metastasized to the brain, and Rakesh Jain’s collaboration with Jeffrey Engelman could well have revealed the mechanism behind therapeutic resistance of brain metastases in HER-2 positive breast cancer.  This breakthrough research “has identified new treatment strategies to overcome this problem which is often lethal to the patients,” says Dr. Jain. “We believe our discovery could have a substantial impact on the future development of therapeutic strategies and ultimately, patient survival from this deadly disease.”

Dr. Jain hopes that clinical trials and future therapeutic strategies for metastatic breast cancer will include HER3 targeted therapies in treating brain metastasis in HER2+ (or PIK3CA mutant) breast cancer.  And since HER3 has been associated with treatment resistance in several types of cancer, this discovery could potentially benefit a much broader group of patients.

“The impact of the microenvironment on tumor growth is a major focus of Rakesh Jain’s research, and NFCR is proud to have supported his research since 1998,” says Franklin C. Salisbury, Jr., Chief Executive Officer of NFCR.  Research cures cancer, and “NFCR’s support of outstanding scientists like Rakesh Jain is making possible whole new approaches to treating cancer, giving hope and promise to patients with cancer.”

About the National Foundation for Cancer Research

The National Foundation for Cancer Research (NFCR) is a leading cancer research charity dedicated to funding cancer research and public education relating to cancer prevention, earlier diagnosis, better treatments and, ultimately, a cure for cancer. NFCR promotes and facilitates collaboration among scientists to accelerate the pace of discovery from bench to bedside. NFCR is committed to Research for a Cure – cures for all types of cancer. For more information, visit http://www.nfcr.org/ or call (800) 321-CURE (2873).

Media Contact:
Hali Hartmann
443 474 6294
hhartmann@nfcr.org

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Party4Life 2016 & the Lucy Fund

Ongoing Fundraising Efforts Seek to Find a Cure for Metastatic Cancer

Over eight years ago, Lucy Stanovick began efforts to educate others about metastatic cancer and fund research to find cures. Her story in terms of an unfortunate diagnosis may be common, but her story of giving and organizing is truly unique. To this day, over $200,000 has been raised in Lucy’s name for the National Foundation for Cancer Research. This is her story…

Lucy’s Story

Lucy Stanovick found out she had Stage IV metastatic breast cancer on April 1, 2008 – she was just 42 years old. Lucy was an English professor, writer, devoted wife and mother of two and she was – understandably – blindsided by this diagnosis. She had always been health-conscious, did self-exams and received yearly mammograms, yet cancer still found its way in. In fact, her previous mammogram in July 2007 came back normal – no signs of cancer. Less than one year later, she was diagnosed with metastatic breast cancer.
Lucy did not sit idly by as she fought her own health battles. For the next four years, Lucy educated the public about metastasis and became involved in initiatives aimed to stop the spread of cancer. It was Lucy’s goal to see metastatic cancer become chronic, not deadly, so that one day when someone you love walks into a doctor’s office and gets told they have metastatic cancer, the prognosis will not be terminal.  Sadly, as the summer of 2012 came to an end, so did Lucy’s life—she passed away at the age of 46.

Lucy’s Legacy

Metastasis causes more than 90% of cancer-related deaths, but receives less than 5% of the funding.

To educate others and raise money for research, Lucy gathered friends and family in 2008 for an all-day, all-night affair she called Party4Life.  Two years later, in partnership with NFCR, Lucy created the Lucy Fund for Metastatic Breast Cancer Research. These efforts have since grown to include even more events and a larger community of supporters dedicated to advancing leading-edge research for metastatic breast cancer.

Lucy selflessly fought for future generations. Her passion lives on and your generous support helps keep her spirit alive.

Party4Life 2016

This year’s Party4Life was hosted by Lucy’s son’s coed service fraternity, Alpha Phi Omega, at his alma mater, Susquehanna University.

Under the leadership of Chapter President Vickie Smith, Party4Life incorporated the theme of Monsters University and featured food, games, speakers, and all around fun!

To support their incredible fundraising efforts and support metastatic cancer research, visit https://www.crowdrise.com/Party4Life.

RESEARCH TO STOP METASTASIS

Dr. Danny Welch directs the NFCR Center for Metastasis Research in its investigations of cancer biology related to metastasis. Dr. Welch and his team have identified genes regulating metastasis, particularly metastasis suppressors; investigated the interactions between metastases and their surrounding tissues, especially for bone metastasis; and are now working to translate their findings into clinical practice.

Through research, they identified genetic changes that predict whether patients will or will not develop metastasis. At least some of these changes occur in mitochondria – where cells convert nutrients into energy. These results could determine that a simple blood draw and analysis of mitochondrial DNA – which is present in every cell and which is small enough to be rapidly analyzed – could be used to help doctors guide their strategies to treat patients.

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Research by NFCR Scientists Reveals New Insights into Treatment Resistance of Metastatic Breast Cancer

Oscillating expression of a key cancer gene may impact treatment approaches for patients

NFCR-supported scientist Dr. Daniel Haber and his team at the Massachusetts General Hospital Cancer Center have identified a dynamic gene expression in metastatic breast cancer that may contribute to disease progression and resistance to treatment experienced by many patients. Tumors can evolve in response to treatment and they may acquire new genetic features that may make them resistant to drugs and cause disease progression.

In their quest to find genetic changes in advanced breast cancer, the scientists utilized the rare circulating tumor cells (CTCs) found in a patient’s bloodstream – which have migrated away from a tumor and into blood vessels. CTCs offer a wealth of information to researchers and oncologists about the state of a patient’s cancer.

“I am thankful to the NFCR for their sustained support of our research to increase our understanding of the genes involved in the progression of cancer and to develop prevention and treatment strategies for metastatic cancer,” said Dr. Haber.

The Haber team used their device, the CTC-iChip, to collect viable CTCs from women initially diagnosed with primary breast tumors that are ER+/HER2-, meaning that their tumor cells expressed estrogen receptor genes (ER+) but did not express the HER2 gene (HER2–). Both ER and HER2 genes are known for their role in fueling breast cancer cells and promoting tumor growth. The patients had undergone multiple courses of treatment for recurrent metastatic cancer.

Intriguingly, molecular characterization of the isolated CTCs revealed not just ER+ / HER2– tumor cells, but also a second type: the ER+ / HER2+ cells that also express the HER2 gene.

Through a series of elegant laboratory experiments, the researchers delved deeper to characterize the CTCs and found a unique and dynamic interconversion of HER2 gene expression: ER+/HER2– cells could spontaneously become ER+/HER2+ and convert back to ER+/HER2–. In addition, researchers found that the two populations of tumor cells depended on different molecular signaling pathways for their proliferation and consequently, were sensitive to different anti-cancer drugs.

Because HER2 gene expression oscillates between on and off spontaneously in these tumors, researchers reasoned that the two separate signaling pathways may need to be simultaneously turned off to halt either cell group from repopulating one another and beginning new abnormal growth. Results of further experiments in cell cultures and more advanced tumor models proved that simultaneous treatment with chemotherapy paclitaxel and targeted therapeutic drugs that inhibit the NOTCH1 molecular signaling pathway achieved suppression of tumor cell growth expressing both ER+ / HER2– and HER2+ subpopulations.

This breakthrough discovery was published in the August 24 online edition of the journal Nature.

“Although more research is needed to uncover why HER2 has this dynamic on-and-off expression, these insights from our research are a positive development for a new treatment approach,” said Dr. Haber.

Dr. Haber also notes that clinical trials will now be needed to test whether these insights from experimental models will translate into better and more effective treatments for women with advanced breast cancer.

“The CTC research platform developed by Dr. Haber and his team continues to produce new knowledge about the intricate ways that cancer may grow and evade treatments,” said Franklin Salisbury, CEO of NFCR. “Metastatic disease causes more than 90% of the fatalities to cancer and the new insights from this research have opened the field for potential new treatment approaches so desperately needed for patients with metastatic breast cancer.”

 

 

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