Nav: Home

A new link between cancer and aging

June 26, 2018

Scientists at Hollings Cancer Center at the Medical University of South Carolina have found that human lung cancer cells resist dying by controlling parts of the aging process, in results published online May 10th in the Journal of Biological Chemistry. The discovery could help us better understand aging and eventually could lead to new treatments for cancer.

Cancer becomes more common as people get older, but scientists are still searching for answers about why this happens. At Hollings Cancer Center, research into the connections between aging and cancer is led by Besim Ogretmen, Ph.D., SmartState Endowed Chair in Lipidomics and Drug Discovery. Ogretmen's team found that cancer cells have specific ways to resist dying the way normal cells do. They do so by protecting the tips of their chromosomes, which hold our DNA, from age-related damage.

Ogretmen studies how cancer cells are different than normal cells to understand how cancer grows and spreads in the body. His work is part of an $8.9 million program project grant to research how alterations of lipid metabolism affect cancer therapy. The grant is helping fund a clinical trial of an anticancer medicine to inhibit cellular signaling that helps cancer survive. The drug was found to be useful against cancer in the research reported in the group's new paper.

As normal cells get older, the tips of their chromosomes, called telomeres, can start to break down, which is a signal for the cell to die. This seems to be part of the aging process in normal cells. However, cancer cells have developed a way to prevent their telomeres from falling apart, which helps them to live much longer than normal cells. The long life of cancer cells is part of what allows them to grow and spread throughout the body.

In their new paper, Ogretmen's research group discovered a specific way that cancer cells escape death in response to telomere damage. Scientists have known that various types of cancer cells have low levels of a protein called p16. Ogretmen's group found that, when telomeres become damaged by age or in response to chemotherapy, p16 is a type of cellular decision-maker, where it helps cells decide to grow older or to simply die.

"Telomeres are like a biological clock for our cells," said Ogretmen. "In cancer, this biological clock is broken."

The researchers found that p16 became most important to cells when their telomeres began to break down. When that happened, p16 rushed into action and pushed cells toward further aging by inhibiting cell death.

To determine the clinical impact of these data, the researchers used a chemical enzyme inhibitor to cause telomere damage in several types of cancer cells, including lung cancer cells. The inhibitor, ABC294640, acts in a way that prevents cancer cells from protecting their telomeres, by inhibiting an enzyme called sphingosine kinase 2. This inhibition was shown to force telomeres to break down.

As a result of this enzyme inhibition, telomeres were damaged, resulting in cancer cell death when p16 levels were low or absent. However, cancer cells with high levels of p16 were able to escape death, and stayed biologically inactive, which was a sign of aging.

"We're excited that there is at least one mechanism that can help us understand how aging is associated with a higher risk of cancer," said Ogretmen. "And then, can we prevent or better treat the aging-related cancers by controlling protective effects of p16 for cancer cell death?"

Ogretmen's group is enthusiastic that the inhibitor in their study might help combat cancer at many levels. The team has already identified the safest dose for use in patients and is planning a phase 2 clinical trial using their inhibitor in patients with a type of liver cancer called hepatocellular carcinoma. The multisite trial will include Hollings Cancer Center, Penn State, the University of Maryland, Mayo Clinic and others.

It is especially important to do this work now, given the predicted forecast by researchers at the National Cancer Institute (NCI) who foresee a 'silver tsunami' of cancer survivors. NCI studies show that by 2040 the number of cancer survivors in the United States will increase by nearly 11 million: from 15.5 million in 2016 to 26.1 million in 2040. A large part of the makeup of the cancer survivor population will shift to older populations. It's estimated that by 2040 only 18 per-cent of cancer survivors will be between ages 50 and 64, and only 8 percent will be younger than 50.

"We hope that maybe we can do both: delay aging and prevent the growth of cancer," said Ogretmen. "That's the ultimate outcome of this."
-end-
About Hollings Cancer Center

The Hollings Cancer Center at the Medical University of South Carolina is a National Cancer Institute-designated cancer center and the largest academic-based cancer research program in South Carolina. The cancer center comprises more than 100 faculty cancer scientists and 20 academic departments. It has an annual research funding portfolio of more than $40 million and a dedication to reducing the cancer burden in South Carolina. Hollings offers state-of-the-art diagnostic capabilities, therapies and surgical techniques within multidisciplinary clinics that include surgeons, medical oncologists, radiation therapists, radiologists, pathologists, psychologists and other specialists equipped for the full range of cancer care, including more than 200 clinical trials. For more information, visit http://www.hollingscancercenter.org

Medical University of South Carolina

Related Cancer Articles:

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.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.