Navigation Links
RLIP76 contributes to pancreatic cancer cell resistance to chemotherapy and radiation
Date:6/19/2012

LAKE TAHOE, Nev. Researchers at the City of Hope Comprehensive Cancer Center have not only identified a protein that allows pancreatic cancer cells to resist therapy but also developed a way to block it, according to results presented at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, held here June 18-21.

"Cancer of the pancreas is notoriously difficult to treat because it usually presents at late stages due to minimal or nonspecific symptoms in the early stages. Thus, surgical treatment is either not possible or fails to cure most patients, resulting in a dismal prognosis 90 percent of patients are likely to die within a year," said Sanjay Awasthi, M.D., professor of medical oncology and therapeutics research, and diabetes, endocrinology and metabolism at City of Hope in Duarte, Calif.

One of the reasons that pancreatic cancer is so difficult to treat is that the tumor cells are largely resistant to the cell death caused by radiation and chemotherapy. Awasthi and colleagues have previously shown that the protein RLIP76 plays a key role in defending cells from other types of cancers from death caused by exposure to chemotherapy or radiation.

"RLIP76 works like an exhaust system," said Awasthi. "It pumps out the toxic chemicals that accumulate in the cancer cell as a result of chemo- or radiotherapy before they can cause cell death."

Now, Awasthi and colleagues have found that there is more RLIP76 in human pancreatic cancer cells than there is in normal human pancreatic cells. Depleting levels of RLIP76 killed human pancreatic cancer cells in culture and shrank established human pancreatic tumors in mice. Moreover, blocking RLIP76 or depleting levels of the protein dramatically enhanced the ability of radiation and the chemotherapeutic agent doxorubicin to destroy human pancreatic cells in culture.

"Pancreatic cancer patients are a special case of the particularly unlucky, and in many ways the most miserable. The drug and radiation resistance of this cancer is legendary," Awasthi said.

"Because we have defined RLIP76 as an essential drug- and radiation-resistance mediating protein, and because blockade of RLIP76 caused regression of less therapy-resistant cancers (lung, colon, breast), as well as equally resistant cancers (kidney, prostate, resistant neuroblastoma), we undertook the present studies to determine whether this treatment could be effective in pancreatic cancer.

"Fortunately, our data show that the seemingly unconquerable pancreatic cancer has an Achilles heel; its toxin exhaust system," he explained. "Moreover, plugging this exhaust caused pancreatic cancer cell death, leaving normal cells relatively unfazed. We hope to translate these studies into clinical trials in the near future."

According to Awasthi, they saw an added benefit to depleting levels of RLIP76 in the mice with established tumors: a decrease in blood sugar, cholesterol and triglycerides. "These findings indicate that it might be possible to develop a single class of medications that have potent antidiabetic and anticancer effects," he said.

Awasthi is the founder of Terapio, which makes the recombinant RLIP76 protein for treatment of radiation poisoning. However, Terapio does not work on the RLIP76-blockading technology that is the crux of the anticancer treatment strategy.


'/>"/>

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

Related medicine news :

1. Stress contributes to cognitive declines in women with breast cancer, researcher says
2. Social-class discrimination contributes to poorer health
3. Short Walks May Ease Fatigue in Pancreatic Cancer Patients
4. Mutant Kras drives pancreatic cancer maintenance via metabolic pathways
5. Early biomarker for pancreatic cancer identified
6. Researchers present new findings for novel pancreatic cancer vaccine
7. Studies See Advances in Detecting, Treating Pancreatic Cancer
8. Nerve growth factors elevated in pancreatic cancer model
9. Sun exposure and sun-sensitive skin type decreased risk for pancreatic cancer
10. Inhibiting Hedgehog signaling pathway may improve pancreatic cancer treatment
11. Study Suggests Vaccine May Help Kids With Brain Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... February 11, 2016 , ... Student-doctors from Western University of ... Program Tuesday, February 9, taking one of the final steps in their medical ... positions across the country. Of the 103 student-doctors who comprise the College of ...
(Date:2/11/2016)... , ... February 11, 2016 , ... Florida Hospital presents ... take on the St. Louis Blues at the Amalie Arena. The puck drops at ... walk-through heart exhibit, the MEGA Heart, prior to the game. The MEGA Heart will ...
(Date:2/11/2016)... ... February 11, 2016 , ... The president released a ... Health System but would shift more of the cost burden to military beneficiaries. ... laid out in the defense budget as including limited quantifiable benefit fixes mixed with ...
(Date:2/11/2016)... Petersburg, FL (PRWEB) , ... February 11, 2016 ... ... providers and advocates will discuss how to improve care by making data on ... pediatric heart disease. The Summit on Transparency and Public Reporting of Pediatric and ...
(Date:2/11/2016)... ... February 11, 2016 , ... Atlantic Information Services, ... Benefit Model: A Case Study for Plans and Purchasers.” Executives from Intel Corp. ... with Intel on value-based health benefits program Connected Care, will discuss the challenges ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)...  Community pharmacists can help improve medication adherence and ... a custom-built medication synchronization program, Cardinal Health MedSync Advantage™. ... Schieber Family Pharmacy in Circleville, ... patients enrolled in this medication synchronization program, which is ... the patient, and it,s a win for us because ...
(Date:2/11/2016)... , Feb. 11, 2016  Delcath Systems, Inc. ... medical device company focused on oncology with an ... liver cancers, announces the engagement of Lars ... Global Medical Consultant. Dr. Birgerson will provide strategic ... clinical operations team to help ensure timely facilitation ...
(Date:2/11/2016)... Scientists from Silicon Biosystems Menarini today ... door to genetic analysis of previously preserved tumor ... isolate with 100 percent purity. Utilizing the com­pany,s ... various stages of development, the researchers were able ... are clinically relevant, and may change the way ...
Breaking Medicine Technology: