Mayo Clinic researchers identify molecule that lays groundwork for development of pancreatic cancer

A research team led by investigators from Mayo Clinic's campus in Jacksonville, Florida, and the University of Oslo, Norway, have identified a molecule that pushes normal pancreatic cells to transform their shape, laying the groundwork for development of pancreatic cancer -- one of the most difficult tumors to treat.

Their findings, reported in Nature Communications, suggest that inhibiting the gene, protein kinase D1 (PKD1), and its protein could halt progression and spread of this form of pancreatic cancer, and possibly even reverse the transformation.

"As soon as pancreatic cancer develops, it begins to spread, and PKD1 is key to both processes. Given this finding, we are busy developing a PKD1 inhibitor that we can test further," says the study's co-lead investigator, Peter Storz, Ph.D., a cancer researcher at Mayo Clinic.

http://www.nature.com/ncomms/2015/150220/ncomms7200/full/ncomms7200.html

Mayo Clinic researchers identify molecule that lays groundwork for development of pancreatic cancer

Two drugs in combination improve survival in patients with advanced pancreatic cancer

In continuation of my update on nab-paclitaxel (stands for nab-nanoparticle albumin-bound) and gemcitabine...

Investigators at the Vall d´Hebron University Hospital and the Vall d'Hebron Institute of Oncology (VHIO), have participated in an international phase III study, published in The New England Journal of Medicine. Results show that administering these two drugs in combination significantly improves one- and two-year survival in patients with advanced pancreatic cancer versus gemcitabine alone, the first-line treatment or most standard approach for this type of cancer to date.

The new drug is set to become a reference in advanced pancreatic cancer treatment. A multicentre phase III study, with centers participating from 11 countries in North America, Europe and Australia, shows that the drug combination nab-paclitaxel and gemcitabine is more effective in the treatment of patients with advanced pancreatic cancer than gemcitabine alone, which has been the standard treatment for these patients up until now.

The clinical trial, sponsored by Celgene Corporation, involved 861 patients, half of whom were administered the nab-paclitaxel/gemcitabine combination, while the other half received gemcitabine alone. Median overall survival was 8.5 months for nab-paclitaxel/gemcitabine versus 6.7 months for gemcitabine alone. One-year survival rates were 35% and 22%, respectively, and two-year survival rates were 9% and 4%, respectively. Similar side effects were found in the new drug and gemcitabine alike. The trial report therefore concluded that the nab-paclitaxel/gemcitabine combination significantly improves overall survival and response rate in patients with advanced pancreatic cancer.

Two drugs in combination improve survival in patients with advanced pancreatic cancer

Bitter melon juice prevents pancreatic cancer in mouse models

"Three years ago researchers showed the effect of bitter melon extract on breast cancer cells only in a Petri dish. This study goes much, much farther. We used the juice  people especially in Asian countries are already consuming it in quantity. We show that it affects the glucose metabolism pathway to restrict energy and kill pancreatic cancer cells," says Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

Agarwal's interest came from connecting the dots of existing research in a novel way. Diabetes tends to presage pancreatic cancer and bitter melon has been shown to effect type-II diabetes, and has been used for centuries against diabetes in the folk medicines of China and India. Following this line of thinking, Agarwal and colleagues wondered what would happen if they closed out the middle man of diabetes and directly explored the link between bitter melon and pancreatic cancer.

The result, Agarwal says, is, "Alteration in metabolic events in pancreatic cancer cells and an activation of the AMP-activated protein kinase, an enzyme that indicates low energy levels in the cells."

Perhaps not coincidentally, bitter melon also regulates insulin secretion by pancreatic beta cells. After studies in cell cultures, the group showed that mouse models of pancreatic cancer that were fed bitter melon juice were 60 percent less likely to develop the disease than controls.

"It's a very exciting finding," Agarwal says. "Many researchers are engineering new drugs to target cancer cells' ability to supply themselves with energy, and here we have a naturally-occurring compound that may do just that."

The Agarwal Lab is now applying for grants that will allow them to move the study of bitter melon into further chemoprevention trials in mouse models of pancreatic cancer.

Ref : dx.doi.org/10.1093/carcin/bgt081

 

Bitter melon juice prevents pancreatic cancer in mouse models

Drug combination extends pancreatic cancer patient survival, study suggests

A multi-center Phase III clinical trial demonstrates that Abraxane (below left structure) (nab-paclitaxel) plus gemcitabine is the first combination of cancer drugs to extend survival of late-stage pancreatic cancer patients compared to standard treatment. Their findings show that Abraxane plus gemcitabine (below right structure) was well tolerated and resulted in clinically meaningful outcomes compared to gemcitabine alone, the current standard of care. 

MPACT is the largest phase III clinical trial completed in advanced pancreatic cancer with more than 800 patients. Findings from the study showed a 59 percent increase in one-year median survival rates from less than a quarter of the patients (22 percent) to more than a third (35 percent). The two-year survival rate for this cancer is negligible, less than 4 percent, but that more than doubles (9 percent) with the nab-paclitaxel/gemcitabine combination.

The study showed significant improvement among some of the sickest patients including those with increased metastases. Significantly there was no increase in life-threatening toxicity. Other drug combinations that have demonstrated benefit have been limited by increased toxicities.

"This is a major improvement in a cancer with the lowest survival rates among all cancer types," said Dr. Ramesh Ramanathan, medical director of Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare and principal investigator for the clinical trial in the United States. "Advanced pancreatic cancer is fourth most common cause of cancer death in the United States and throughout the world. It is difficult to diagnose with a majority of the cases diagnosed at a late stage after the disease has already advanced."

Drug combination extends pancreatic cancer patient survival, study suggests

Combination [of Vismodegib (GDC-0449) and Gemcitabine] therapy may help defeat pancreatic cancer

 In continuation of my update on (GDC-0449) Visodegib and Gemcitabine

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.

Combination therapy may help defeat pancreatic cancer

Rigosertib drug shows promise against advanced pancreatic cancer

Researchers from University of Colorado, lead by Antonio Jimeno, have found that, a new drug, Rigosertib,  allows pancreatic cancer cells to rush through replication - and then stops them cold, killing them in in the middle of a step called M phase. Healthy cells that don't rush are unharmed.

Data from a phase I clinical trial of patients with advanced pancreatic cancer and additional solid tumors recently published in the journal Clinical Cancer Research shows the strategy has promise. While the goal of any phase I trial is to establish the dosage that best balances effectiveness against side effects, 11 of the 19 patients treated achieved stable disease, which lasted for a median of 113 days.

"Really, the drug takes one of cancer's greatest strengths and turns it into a weakness," says Wells Messersmith, MD, co-leader of the Developmental Therapeutics Program at the University of Colorado Cancer Center and the clinical trial's national principal investigator.

Instead of going with the flow of the natural cell cycle, cancer cells amplify two signals - PLK1 and PI3K - which allows them to blast through the cell cycle and divide much more quickly. In the process, they break this step of the natural cell cycle, known as the G1 regulatory mechanism, and thus depend on the kick of PLK1 and P13K to push at a frenzied pace through replication...

More...

ESPAC-3 trial (Fluorouracil and Folinic Acid) shows promising results to prevent pancreatic cancer

In continuation of my update on  drug discovery and 5-fluorouracil

A major international trial has shown a commonly used chemotherapy drug, 5-fluorouracil, and  Folinic Acid  is as effective at helping prevent pancreatic cancer returning after surgery as the more expensive standard chemotherapy treatment.

The results of the Cancer Research UK- funded study mean the cheaper drug - called 5-fluorouracil (5-FU) - could be prescribed in cases when the standard chemotherapy - gemcitabine - has failed, providing an extra lifeline for patients whose cancer comes back after surgery.

They also raise hopes that a new trial currently underway, looking at combining an oral version of 5-FU with the standard treatment of gemcitabine, could lead to a more effective treatment for pancreatic cancer patients who are eligible for surgery.

The trial, called European Study Group for Pancreatic Cancer (ESPAC)-3, is the largest of its kind and involved 159 centres in Europe, Australasia, Japan and Canada which between them recruited 1088 patients who had undergone surgery for pancreatic cancer.

One group had the standard chemotherapy treatment - gemcitabine. The second group had a cheaper widely available drug called 5-fluorouralcil (5-FU) that is commonly used in cancer treatment already.

The results mean that 5-FU should now also be considered one of the standard options for the treatment of patients with this disease.

They build on earlier trial results suggesting patients who had surgery and chemotherapy had better a chance of survival than patients who only had surgery. 

Finding out these two drugs are as effective as each other at preventing pancreatic cancer returning after surgery is important. It raises hopes that a new trial currently looking at giving two similar drugs together could be successful at preventing or at least delaying pancreatic cancer returning after surgery.

"Previous trial results involving advanced pancreatic cancer patients have shown this drug combination can give precious extra months or even years of life, so there is reason to be hopeful the survival benefit could be even more marked for patients who are eligible for surgery."

 Ref : http://jama.ama-assn.org/cgi/content/full/304/10/1073

Clinical Trial Confirms Single-Agent Efficacy of Rexin-G in Metastatic Pancreas Cancer...

Epeius Biotechnologies, confirms the first real breakthrough for pancreatic cancer seen in years; publishes a landmark report of tumor-targeted Rexin-G as stand-alone therapy in chemotherapy-resistant pancreatic cancer.

By meeting all primary and secondary study endpoints of safety and efficacy, Rexin-G has succeeded in an area of clinical oncology where many promising biologics have simply failed to deliver. By achieving both progression-free survival and overall survival benefits in pancreas cancer, while avoiding untoward systemic or dose-limiting toxicities, Rexin-G has raised the bar for the entire biopharmaceutical industry, as it inaugurates the emerging field of precision-targeted genetic medicine. The outstanding results of this advanced U.S. clinical trial confirm the results of previous preclinical and clinical studies conducted in the Philippines (where Rexin-G is approved for all solid tumors), and demonstrate beyond contestation that Rexin-G, at these effective dose levels, exhibits profound anti-tumor activity when administered as a single therapeutic agent in otherwise intractable Stage IV pancreatic cancer..

Interested one can see the mechanism of action ib this video.

Ref : http://www.epeiusbiotech.com/press-101409.asp