Monthly Archives: January 2016

How certain drugs alter metabolism of pancreatic cancer cells

UT Southwestern Medical Center researchers have found that cancer drugs known as CDK4/6-inhibitors alter the metabolism of pancreatic cancer cells, revealing a biologic vulnerability that could be exploited for therapeutic gain. The findings were published today in Cell Reports.

Because pancreatic cancer has one of the worse prognoses of any cancer and is the third leading cause of cancer deaths in the U.S., according to the National Cancer Institute, researchers for years have sought to find better treatment options.

Last year, the FDA approved the first cyclin-dependent kinase 4/6 (CDK4/6) inhibitor for treating a certain type of advanced breast cancer. This class of drugs has been widely studied in clinical trials for many other types of cancer, including pancreatic cancer. CDK 4/6 inhibitors are cytostatic, meaning they work by preventing cancer cells from growing and dividing.

“On the one hand, that’s great, because the tumor won’t grow, but on the other hand, the patient still has a tumor, which will eventually become resistant to those drugs,” said study senior author Dr. Erik Knudsen, Professor of Internal Medicine in the Eugene McDermott Center for Human Growth and Development at UT Southwestern.

“There’s a lot of interest in better understanding the biology behind CDK4/6 inhibitors — and in finding out whether we can use that information to kill tumors instead of simply stopping their growth,” added Dr. Agnieszka Witkiewicz, also in the McDermott Center and an Associate Professor of Pathology.

In this study, the research team treated human pancreatic cancer cells and tumors grown in mice with CDK4/6-inhibiting drugs. Surprisingly, they found that when tumor cells were treated with CDK4/6 inhibitors, the cells’ metabolism — the way cancer tumors get energy — became more active.

“Now we can try attacking specific aspects of CDK4/6-induced metabolic programming,” said Dr. Knudsen, also a member of UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, along with Dr. Witkiewicz. “For example, by targeting altered tumor metabolism, we could potentially turn the cytostatic effect of CDK4/6 inhibitors into a cytotoxic effect that actually kills the cancer cells.”

The upshot is that by disrupting a tumor’s cell cycle with CDK4/6 inhibitors and then targeting the altered metabolism with other drugs — such as mTOR inhibitors — it may be possible to positively impact cancer treatment.

“These data yield valuable new insights into the cross talk between CDK inhibitors, signaling pathways, and tumor metabolism in pancreatic cancer, opening up some interesting new possibilities for treatment that could be evaluated in clinical trials,” Dr. Witkiewicz said. “The real goal is that this work — as well as ongoing studies — will benefit patients with pancreatic cancer.”

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*credit verbatim via provided by UT Southwestern Medical Center


Scientists discover how diabetes drug Metformin slows down pancreatic cancer

Researchers at the Massachusetts General Hospital (MGH) might have stumbled upon the mechanism of how the diabetes drug metformin can slow down the progression of cancer of the pancreas.

The details of the study are published in the journal PLOS One, where the team describes that this common diabetes drug decreases the inflammation and fibrosis seen commonly in pancreatic cancer. However, based on their findings in patient tumor samples as well as cellular and animal models, the researchers add that in overweight and obese patients might benefit more from this surprising metformin discovery.

The study focused on the most commonly occuring pancreatic cancer – pancreatic ductal adenocarcinoma (PDA) – which kills almost 40,000 people in the U.S. ever year. Half of those diagnosed with PDA are overweight or obese, and almost 80 percent are insulin resistant or have type 2 diabetes.

Previous analyses have revealed that Diabetic patients taking metformin have a lower risk of developing PDA; and those who do have PDA have a reduced fatality rate. But before the current study nobody knew how or why this drug inhibited the progress of pancreatic cancer.

The team discovered that metformin increases a collection of tumor-associated immune cells and a dense connective tissue which are both characteristic of pancreatic cancer. According to the lead author of the study, Dai Fukumura, MD, PhD, of the Steele Laboratory of Tumor Biology in the MGH Department of Radiation Oncology, metformin does this by slowing down the activation of the pancreatic stellate cells (cells that cause fibrosis and interact closely with cancer cells to create a tumor friendly environment) and by reprogramming immune cells to reduce inflammation.

However the team observed that hat these changes were more pronounced in the tumors of obese and overweight individuals, in whom the tumors had increased fibrosis.

In fat mice, the researchers found that metformin treatment reduced levels of tumor-associated macrophages by 60 percent. The tumors of animals treated with metformin also had showed a reduction in metastasis, suggesting a lower risk in the spread of the cancer.

This new evidence is part of a wave of findings that suggest that regular everyday drugs can play a huge role in preventing and fighting cancer. In fact an organization called ReDo has been set up solely for this purpose of finding regular drugs with anti-cancer properties.

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*credit verbatim via and Mohan Garikiparithi*

Merck, BioLineRX to study drug combo to fight #PancreaticCancer

Israeli biopharmaceutical company BioLineRX Ltd said on Tuesday it would collaborate with U.S. industry heavyweight Merck to test a combination of drugs for the treatment of pancreatic cancer.

The companies will partner in a mid-stage study to evaluate the safety and efficacy of the combination of BioLineRx’s BL-8040 and Merck’s Keytruda in patients with metastatic pancreatic adenocarcinoma.

“Because certain tumors exhibit only a modest response to existing immunotherapies, we are increasingly seeing clinical studies involving combinations of immuno-oncology agents with other classes of drugs,” said Kinneret Savitsky, BioLineRx’s chief executive.

BL-8040 acts against CXCR4 receptors that are involved in tumor progression, the company said. It has been shown in several clinical trials to mobilize immune cells and to be effective at inducing direct tumor cell death.

Keytruda, an antibody, works by increasing the ability of the body’s immune system to help detect and fight tumor cells, said Merck, which is known as MSD outside the United States and Canada.

Pancreatic adenocarcinoma accounts for most cases of pancreatic cancer, according to the American Cancer Society. Specific symptoms often do not develop until the disease has reached an advanced stage, which is reflected in a low five-year survival rate.

The study is due to start by mid-2016 and both companies will have the option to expand the collaboration to include a pivotal registration study, BioLineRX said.

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*credit verbatim via , Ari Rabinovitch, reporter; David Clarke, editing*



More magnesium may lower risk of pancreatic cancer

Magnesium intake may be an effective way to prevent pancreatic cancer, a new study suggests.

Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women in the United States. The overall occurrence of pancreatic cancer has not significantly changed since 2002, but the mortality rate has increased annually from 2002 to 2011, according to the National Cancer Institute.

“Pancreatic cancer is really unique and different from other cancers,” says Ka He, chair of the epidemiology and biostatistics department at Indiana University. “The five-year survival rate is really low, so that makes prevention and identifying risk factors or predictors associated with pancreatic cancer very important.”

Previous studies have found that magnesium is inversely associated with the risk of diabetes, which is a risk factor of pancreatic cancer. But few studies have explored the direct association of magnesium with pancreatic cancer and those that did had inconclusive findings, says lead author Daniel Dibaba, a PhD student in the School of Public Health.

Using information from the VITamins and Lifestyle study, the researchers analyzed an enormous trove of data on more than 66,000 men and women, ages 50 to 76, looking at the direct association between magnesium and pancreatic cancer and whether age, gender, body mass index, non-steroidal anti-inflammatory drugs use, and magnesium supplementation play a role.

Of those followed, 151 participants developed pancreatic cancer. Every 100-milligrams-per-day decrease in magnesium intake was associated with a 24 percent increase in the occurrence of pancreatic cancer.

The study, published in the British Journal of Cancer, also found that the effects of magnesium on pancreatic cancer did not appear to be modified by age, gender, body mass index, or non-steroidal anti-inflammatory drug use, but was limited to those taking magnesium supplements either from a multivitamin or individual supplement.

“For those at a higher risk of pancreatic cancer, adding a magnesium supplement to their diet may prove beneficial in preventing this disease,” Dibaba says.

“While more study is needed, the general population should strive to get the daily recommendations of magnesium through diet, such as dark, leafy greens or nuts, to prevent any risk of pancreatic cancer.”

Other researchers from Indiana University and from the University of Washington, and the Jikei University School of Medicine in Tokyo contributed to the study.

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* credit verbatim via and
April Toler of Indiana University *