Focus on Cancer RSS Feed 2014-10-16 09:30:00

Penn’s Abramson Cancer Center and the Caring for Carcinoid Foundation are teaming up to provide a free day-long neuroendocrine tumor conference for patients and caregivers.

This free educational conference highlights news in NET diagnosis, disease and symptom management and panel discussion.

Attendees will receive the latest information about research, treatment advances, clinical trials, and survivorship issues.

Who Should Attend?

This session can be helpful for those newly diagnosed, currently in treatment, or who are long-term survivors; as well as family members and caregivers of those affected by:

  • Gastrointestinal tract NETs including:
    • Pancreatic NETs (hereditary or sporadic) 
    • Zollinger-Ellison syndrome (gastrinomas)
    • Insulinomas
    • Alimentary tract NETs (foregut, midgut or hindgut)
    • Functional (carcinoid syndrome)
    • Non-functional
  • Bronchial, thymic and carcinoid in other locations
  • Pheochromocytomas and paragangliomas including hereditary and sporadic forms 
  • Hereditary Ssyndromes associated with neuroendocrine tumors

4th Focus On Neuroendocrine Tumors Conference

Date: Friday, October 24, 2014
Time:  8 am to 2:30 pm
Location: Hilton Hotel, 4200 City Avenue, Philadelphia, PA

RSVP for the Focus on Neuroendocrine Tumor Conference here.

Can’t Make the Conference? 

If you can’t make this year’s conference, you can watch or follow the conference live:

October 24: Focus On Neuroendocrine Tumors Conference

Penn’s Abramson Cancer Center and the Caring for Carcinoid Foundation are teaming up to provide a free day-long neuroendocrine tumor conference for patients and caregivers.

This free educational conference highlights news in NET diagnosis, disease and symptom management and panel discussion.

Attendees will receive the latest information about research, treatment advances, clinical trials, and survivorship issues.

Who Should Attend?

This session can be helpful for those newly diagnosed, currently in treatment, or who are long-term survivors; as well as family members and caregivers of those affected by:

  • Gastrointestinal tract NETs including:
    • Pancreatic NETs (hereditary or sporadic) 
    • Zollinger-Ellison syndrome (gastrinomas)
    • Insulinomas
    • Alimentary tract NETs (foregut, midgut or hindgut)
    • Functional (carcinoid syndrome)
    • Non-functional
  • Bronchial, thymic and carcinoid in other locations
  • Pheochromocytomas and paragangliomas including hereditary and sporadic forms 
  • Hereditary Ssyndromes associated with neuroendocrine tumors

4th Focus On Neuroendocrine Tumors Conference

Date: Friday, October 24, 2014
Time:  8 am to 2:30 pm
Location: Hilton Hotel, 4200 City Avenue, Philadelphia, PA

RSVP for the Focus on Neuroendocrine Tumor Conference here.

Can’t Make the Conference? 

If you can’t make this year’s conference, you can watch or follow the conference live:

Targeting the c-Met/FZD8 Axis Eliminates HNCSCs

Cancer stem–like cells (CSC) thought to contribute to head and neck squamous carcinomas (HNSCC) may offer attractive therapeutic targets if a tractable approach can be developed. In this study, we report that silencing c-Met is sufficient to suppress sphere formation, tumor initiation, and metastatic properties of HN-CSC. Pharmacologic inhibition of c-Met with the selective inhibitor PF-2341066 preferentially targeted CSC and synergized with conventional chemotherapy to improve efficacy in a mouse xenograft model of HNSCC, impeding tumor growth and reducing metastasis. Mechanistic investigations showed that CSC elimination was due to downregulation of Wnt/β-catenin signaling in HN-CSC and that the Wnt pathway receptor FZD8 was essential for interactions of c-Met and Wnt/β-catenin signaling in HN-CSC. Notably, ectopic expression of FZD8 rescued the impaired phenotype of HN-CSC where c-Met was inhibited. Furthermore, c-Met upregulated FZD8 through the ERK/c-Fos cascade in HN-CSC. Taken together, our results offer a preclinical proof-of-concept for targeting the c-Met/FZD8 signaling axis as a CSC-directed therapy to improve HNSCC treatment. Cancer Res; 74(24); 1–14. ©2014 AACR.

Targeting the c-Met/FZD8 signaling axis eliminates patient-derived cancer stem-like cells in head and neck squamous carcinomas

Cancer stem-like cells (CSC) thought to contribute to head and neck squamous carcinomas (HNSCC) may offer attractive therapeutic targets if a tractable approach can be developed. In this study, we report that silencing c-Met is sufficient to suppress sphere formation, tumor initiation and metastatic properties of HN-CSC. Pharmacologic inhibition of c-Met with the selective inhibitor PF-2341066 preferentially targeted CSC and synergized with conventional chemotherapy to improve efficacy in a mouse xenograft model of HNSCC, impeding tumor growth and reducing metastasis. Mechanistic investigations showed that CSC elimination was due to downregulation of Wnt/β-catenin signaling in HN-CSC and that the Wnt pathway receptor FZD8 was essential for interactions of c-Met and Wnt/β-catenin signaling in HN-CSC. Notably, ectopic expression of FZD8 rescued the impaired phenotype of HN-CSC where c-Met was inhibited. Furthermore, c-Met upregulated FZD8 through the ERK/c-Fos cascade in HN-CSC. Taken together, our results offer a preclinical proof-of-concept for targeting the c-Met/FZD8 signaling axis as a CSC-directed therapy to improve HNSCC treatment.

MT4-MMP/EGFR Axis Triggers Tumor Growth

MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol–anchored matrix metalloprotease expressed on the surface of cancer cells that promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGFα and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expressions were correlated in human triple-negative breast cancer specimens. Altogether, our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. Cancer Res; 74(23); 1–13. ©2014 AACR.