Navigation Links
Inhibiting Hedgehog signaling pathway may improve pancreatic cancer treatment
Date:6/19/2012

LAKE TAHOE, Nev. Combining a new targeted therapy with standard chemotherapy may help defeat pancreatic cancer, according to results presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, held here June 18-21.

"We believe that GDC-0449 has the potential to change the approach to treating pancreatic cancer," said Edward J. Kim, M.D., Ph.D., a medical oncologist at the University of Michigan Comprehensive Cancer Center in Ann Arbor, Mich.

GDC-0449 targets the Hedgehog signaling pathway. This pathway is normally silent in the adult pancreas but it is switched on in patients with pancreatic cancer and contributes to the desmoplastic stroma that is characteristic of this disease.

"This dense stroma is believed to contribute to resistance to chemotherapy by presenting a physical barrier to chemotherapy delivery," Kim explained.

In addition, Hedgehog levels are increased in pancreatic cancer stem cells. Cancer stem cells are a subset of cancer cells present in a tumor that are believed not only to drive tumor growth by generating bulk tumor cells, but to also be particularly resistant to standard therapies like chemotherapy and radiation.

"Even if a therapy succeeds in obtaining a response, cancer stem cells may persist and contribute to resistance and progression of disease," Kim said. "Having found that pancreatic cancer stem cells have higher Hedgehog levels than bulk cancer cells, we were interested in determining whether targeting the Hedgehog signaling pathway and, therefore, the cancer stem cells might lead to improved outcomes in pancreatic cancer."

GDC-0449 targets the Smoothened (SMO) protein in the Hedgehog signaling pathway. It was approved for use in basal cell carcinoma and is marketed as vismodegib. Kim and his colleagues felt that treating patients with pancreatic cancer first with GDC-0449 and then with the standard chemotherapeutic drug gemcitabine might disrupt the desmoplastic stroma and improve the efficacy of the chemotherapy.

They evaluated this strategy in treatment-naive patients with advanced pancreatic cancer. Patients underwent needle biopsies of the cancer before and after taking GDC-0449 for three weeks to study the effects of GDC-0449 on the Hedgehog pathway signals, tumor stroma and pancreatic cancer stem cells. Gemcitabine was added to GDC-0449 following the second biopsy.

Five patients achieved partial response, and another four patients had stable disease, yielding a 50 percent progression-free survival rate at three months.

"New ways to treat pancreatic cancer are needed to improve response to therapy and ultimately patient outcomes," Kim said, adding that he hopes data from the biopsy specimens will help identify predictive markers to determine who would benefit from this combination treatment.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Cellular pathway linked to diabetes, heart disease
2. Unusual protein helps regulate key cell communication pathway
3. Mutant Kras drives pancreatic cancer maintenance via metabolic pathways
4. Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved
5. VCU researchers identify changes in cholesterol metabolic pathways
6. Researchers determine pathway for origin of most common form of brain and spinal cord tumor
7. Clinical insight improves treatment with new lung cancer drug
8. Improved Stem Cell Line May Avoid Tumor Risk: Study
9. Normalizing tumor blood vessels improves delivery of only the smallest nanomedicines
10. Exercise improves quality of life during breast cancer treatment
11. IU, Regenstrief automated system aims to improve child health
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2017)... , ... June 24, 2017 , ... The weather is ... time outdoors. Home and business owners should be aware that the summer months provide ... In fact, mechanical locks and keys can be negatively affected from direct exposure to ...
(Date:6/23/2017)... ... June 23, 2017 , ... The Rhode ... of Care Management Alerts and Dashboards, an innovative new service enabling healthcare providers ... RIQI’s Care Management Alerts and Dashboards provide near real-time data about patients admitted ...
(Date:6/23/2017)... ... June 23, 2017 , ... By scoring 100% for fiscal management and accountability, ... premier online charity evaluator, Charity Navigator, validating ANRF's work as a top charity in ... by Charity Navigator and earns ANRF a spot on their “ 10 Charities Worth ...
(Date:6/23/2017)... ... ... Studies show evidence that carotenoids and antioxidants derived either from the diet ... , But how often do ophthalmologists and optometrists in Sweden recommend the use of ... with early symptoms of AMD? A study published recently in Dove Medical ...
(Date:6/23/2017)... ... June 23, 2017 , ... Dr. Ran Y. Rubinstein ... recently begun offering three new minimally invasive procedures to patients who want a ... downtime, Dr. Rubinstein is excited to bring microneedling, microneedling facials, and platelet rich ...
Breaking Medicine News(10 mins):
(Date:6/7/2017)... 2017  Diplomat Specialty Infusion Group, a brand of Diplomat Pharmacy, ... Iowa location. The ... features an ISO 7 cleanroom—the standard needed to compound intravenous (IV) ... level of pollutants. "Our new ... better serve our Iowa patients," said ...
(Date:6/1/2017)... , June 1, 2017 Nutriceutical Holdings ... Veterinarian Recommended Solutions (VRS), and KD Pharma Group have ... Nutriceutical Holdings by KD Pharma Group. KD Pharma Group ... the option to acquire the entire company. ... KD. They are committed to growing the NH companies ...
(Date:5/26/2017)... 26, 2017  Endo International plc (NASDAQ: ENDP ... CEO, will represent the Company in a fireside chat at ... Tuesday, June 13, 2017 at 10:40 a.m. PT / 1:40 ... in Rancho Palos Verdes, CA. ... will be available on the Company,s website at http://www.endo.com/investors/overview ...
Breaking Medicine Technology: