Nav: Home

Overcoming resistance in pancreatic cancer

September 09, 2019

Cold Spring Harbor, NY -- Cancer is relentless and resilient. When a drug blocks a cancer cell's main survival pathway, the cell avoids the obstacle by taking different pathways or detours to save itself. This tactic is called "developing resistance," and it's one of the key challenges researchers face when seeking effective therapeutics to combat pancreatic ductal adenocarcinoma (PDA).

A group of researchers at Cold Spring Harbor Laboratory (CSHL) has now found a way to tackle this problem and stop the growth of pancreatic tumors in mice. Their findings are published in the journal Clinical Cancer Research.

Pancreatic cancer has a five-year survival rate of only 8 percent. Professor David Tuveson's lab at CSHL is focused on identifying better treatment strategies to help prolong survival for patients, including new drugs that can be introduced into clinical trials.

More than 90 percent of pancreatic cancer patients carry a mutation, which controls cell growth and death, in the cancer-causing gene KRAS. The KRAS oncogene is difficult to drug directly, so researchers are testing indirect routes to shutting it down. One approach targets the AKT and MAP-Kinase (MAPK) downstream signaling pathways that support KRAS.

"Some clinical trials have targeted these pathways, but high toxicity levels and therapeutic resistance development precluded further investigation of these regimens," said Youngkyu Park, a Research Investigator in the Tuveson lab. "Toxicity can occur when anti-tumor agents aren't malignancy-specific. That means they risk killing healthy cells as well."

The Tuveson lab encountered the problem of resistance pathways when it tried to barricade both the AKT and MAPK pathways in PDA.

To develop an effective cancer drug, the team created drug cocktails that block both the main pathways supporting pancreatic cancer cell growth and cancer cell-specific resistance pathways.

By culturing normal human cells and cancer cells in 3D organoid models and testing them concurrently, the team was able to distinguish particular signaling mechanisms that only affected pancreatic cancer cells. This allowed them to pinpoint the ERBB signaling pathway as the pancreatic cancer-specific resistance mechanism following AKT/MAPK blockade.

By inhibiting ERBB signaling in addition to MAPK signaling, the researchers observed pancreatic tumors shrink in organoid mouse model of PDA.

"We hope this study will help other research groups to use the same methodological approach we use in the paper," said Mariano Ponz-Sarvisé, a former CSHL Clinical Fellow and an author on the study. "I believe that for some drugs, this approach can help find new avenues to overcome resistance."
-end-
About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory's education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle and high school students and teachers. For more information, visit http://www.cshl.edu

Cold Spring Harbor Laboratory

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.