Research

Starving pancreatic cancer as a new technique for treatment

Researchers are pursuing a new therapeutic target to kill pancreatic cancer cells


By Shanley Pierce | August 5, 2019

Pancreatic cancer cells are cloaked in a protective shield that blocks drug therapies from penetrating their surface, making pancreatic cancer extremely difficult to treat. But a team of researchers at The University of Texas MD Anderson Cancer Center has discovered a potential approach that would essentially “starve” these cancer cells to death.

Successful therapies that target the molecular pathways of pancreatic cancer are scarce. In a recent study published in Nature, researchers sought to understand how all proteins on the surface of pancreatic cancer cells are rearranged and how that regrouping affects tumor cell growth.

Very often, researchers will focus on one particular gene protein, said the study’s senior author, Giulio Draetta, M.D., Ph.D., chief scientific officer and professor of genomic medicine at MD Anderson. But this time, Draetta and his team took the opposite approach.

“We asked, instead: can we look at anything that is expressed there on every pancreatic tumor cell?” Draetta explained.

By doing so, he and his team discovered that a particular protein, syndecan 1 (SDC1), mobilizes to the cell surface after receiving a signal transmitted from a mutated oncogene, KRAS. When KRAS functions normally, it regulates cell growth; however, when it becomes mutated, its signaling goes haywire and causes an uncontrolled overgrowth of cells—oftentimes leading to the development of cancer.

The American Cancer Society estimates approximately 56,770 Americans will be diagnosed with pancreatic cancer in 2019. The five-year survival rate is 9 percent.

A certain subtype of pancreatic cancer known as pancreatic ductal adenocardinoma (PDAC), which makes up 90 percent of all pancreatic cancers, is particularly devastating. Standard treatments for PDAC include surgery, radiation, chemotherapy and immunotherapy, but because it is one of the most chemo-resistant cancers, prognosis remains bleak. The five-year PDAC survival rate hovers between 5 and 7 percent, according to a paper published in the International Journal of Molecular Sciences.

The protein KRAS is present in nearly all cases of PDAC.

Whack-a-mole
After determining that KRAS and SDC1 proteins play an integral role in pancreatic cancer, Draetta and the team set about understanding how KRAS drives the aggressive growth of pancreatic tumors.

“What we found is that it’s really responsible for allowing these tumor cells to feed themselves by using a mechanism called macropinocytosis,” he explained.

Macropinocytosis, also referred to as “cell drinking,” is the mechanism cells use to gulp up surrounding molecules, nutrients and antigens.

“Basically, they can take proteins from the outside environment and use them as food,” Draetta said.

No current drug therapy can starve pancreatic cancer cells. KRAS is “one of the most elusive targets in cancer research” and has earned a reputation as an “undruggable” protein, according to the National Cancer Institute.

The findings of Draetta and his team open the door for future studies to target KRAS and SDC1 to cut off the food supply of these cancer cells.

Ultimately, curing cancer is going to take a combined approach, Draetta said.

“The moment you block something, the cancer cells come up with something else,” he added. “Sometimes we think of cancer cells as a whack-a-mole game—you hit them somewhere and something else pops up, so the more agents they put forward that are hitting different components of the pathways, the more there is a chance that in combination they might actually overcome this resistance mechanism because you are going to limit the ability for them to escape.”

Draetta approaches the possibility of developing a new KRAS-targeted therapeutic with cautious optimism.

“I’m trying to keep everybody honest in terms of publishing solid observations and be able to think about translation … as opposed to pretending that everything we discover and publish is made true,” he said. “We try to find a different way and really focus on things that provide high promise. This is because we owe it to our patients.”




Social Posts

profile_image

Harris Health System

@harrishealth

Happy Fall! https://t.co/wjF8teaVxm

14 mins ago
profile_image

Texas Children's

@TexasChildrens

Learn more about the rise of the anti-vaccination movement in @TexasChildrens second season of Outcomes. Listen here: https://t.co/4a9hcW4WyQ #OutcomesPodcast #TexasChildrens https://t.co/MxsKLH8Ory

20 mins ago
profile_image

TexasHeartInstitute

@Texas_Heart

RT @MoveItMonday: You don't have to leave your chair to #MoveItMonday! Try these three simple chair yoga exercises to stretch away stress,…

26 mins ago
profile_image

University of Houston

@UHouston

RT @houstonalumni: Naming the mascot “Shasta” was an idea that came in 1947 when Alpha Phi Omega service fraternity bought UH’s first live…

31 mins ago
profile_image

MD Anderson Cancer Center

@MDAndersonNews

#Clinicaltrials are at the core of our mission to #endcancer. Learn from our Dr. Patrick Hwu how they help us discover new treatments to benefit future and current patients: https://t.co/ENqWbPrvNt https://t.co/Jkuu9JlXbg

39 mins ago
profile_image

Veterans Affairs

@DeptVetAffairs

Today’s #VeteranOfTheDay is Army Veteran Charles J. Gestrich, who served as a railway mail clerk during the Korean War from 1951 to 1953: https://t.co/6mzBvGdZtR

52 mins ago
profile_image

Veterans Affairs

@DeptVetAffairs

@USMC Veteran Kionte lost his leg in an IED blast. During recovery, he experienced depression and sought support. Visit https://t.co/tBxE005jeW to hear more about Kionte’s journey back to physical and mental health.

1 hour ago
profile_image

Rice University

@RiceUniversity

Malawi’s national adoption of affordable neonatal CPAP technology developed at @Rice360atRiceU resulted in sustained improvements in the survival of babies with respiratory illness, according to a new study in the journal Pediatrics. https://t.co/mYtNlEf8uz

1 hour ago
profile_image

Veterans Affairs

@DeptVetAffairs

@USMC Veteran Kionte lost his leg in an IED blast. During his recovery, he experienced depression and sought support. Visit https://t.co/tBxE005jeW to hear more about Kionte’s journey back to physical and mental health.

1 hour ago
profile_image

Rice University

@RiceUniversity

RT @RiceUNews: Here's to 10 years of fun and fitness!@ricerec is celebrating its 10th anniversary with a week of events, starting today…

1 hour ago
profile_image

BCMHouston

@bcmhouston

Happy 20th Birthday to the Baylor International Pediatric AIDS Initiative! Find out how this program has grown over the last two decades. https://t.co/S5PSODwhVt #BIPAI

1 hour ago
profile_image

Houston Methodist

@MethodistHosp

@lesmiskid @blummer27 @JuliaMorales @RealToddKalas @astros Thanks for sharing this great pic!

2 hours ago
profile_image

MD Anderson Cancer Center

@MDAndersonNews

How researchers, led by our Dr. Rodabe Amaria, are working to make pre-surgical treatment an option for more #melanoma patients: https://t.co/ljUwUPQxav #endcancer

2 hours ago
profile_image

BCMHouston

@bcmhouston

Each year, our faculty and staff are given a work day to pursue a volunteer activity they are passionate about. Learn about some of their experiences. https://t.co/xErhwmEeds #volunteering #community https://t.co/uupd0H3YVS

3 hours ago
profile_image

Rice University

@RiceUniversity

RT @RiceUNews: Wondering about the new #art going up inside Brochstein Pavilion this week?It's the first in @RiceUniversity Public Art’s…

3 hours ago