Compound stimulates tumor-fighting protein in cancer therapy

February 06, 2013

HERSHEY, Pa. --A compound that stimulates the production of a tumor-fighting protein may improve the usefulness of the protein in cancer therapy, according to a team of researchers.

TRAIL is a natural anti-tumor protein that suppresses tumor development during immune surveillance -- the immune system's process of patrolling the body for cancer cells. This process is lost during cancer progression, which leads to uncontrolled growth and spread of tumors.

The ability of TRAIL to initiate cell death selectively in cancer cells has led to ongoing clinical trials with artificially created TRAIL or antibody proteins that mimic its action. Use of the TRAIL protein as a drug has shown that it is safe, but there have been some issues, including stability of the protein, cost of the drug, and the ability of the drug to distribute throughout the body and get into tumors, especially in the brain.

"The TRAIL pathway is a powerful way to suppress tumors but current approaches have limitations that we have been trying to overcome to unleash an effective and selective cancer therapy," said Dr. Wafik El-Deiry, professor of medicine and chief of the hematology/oncology division, Penn State College of Medicine. "The TRAIL biochemical cell death pathway naturally lends itself as a drug target to restore anti-tumor immunity."

Researchers have identified a compound called TRAIL-inducing Compound 10 (TIC10) as a potential solution. TIC10 stimulates the tumor suppression capabilities of TRAIL in both normal and tumor tissues, including in the brain, and induces tumor cell death in mice. They report their findings in the journal Science Translational Medicine.

TIC10 is a small molecule. This organic compound binds to a protein and alters what the protein does.

Stimulation of TRAIL protein is sustained in both tumor and normal cells, with the normal cells contributing to the TIC10-induced cancer cell death through a bystander effect. It is effective in cancer cell samples and cell lines resistant to conventional therapies.

"I was surprised and impressed that we were able to do this," El-Deiry said. "Using a small molecule to significantly boost and overcome limitations of the TRAIL pathway appears to be a promising way to address difficult to treat cancers using a safe mechanism already used in those with a normal effective immune system. This candidate new drug, a first-in-its-class, shows activity against a broad range of tumor types in mice and appears safe at this stage."

New treatments are needed for advanced cancer, as more than half a million people in the United States will die of cancer in 2013.

"We have enough preclinical information to support the rationale for testing this new drug in the clinic," El-Deiry said.

TIC10 seems to be nontoxic to normal cells or mice even at doses 10 times higher that an observed therapeutic dose. However, more research needs to be completed to satisfy FDA requirements prior to initiation of clinical testing.
-end-
Other researchers are Joshua E. Allen, David T. Dicker, Akshal S. Patel, Nathan G. Dolloff, Kimberly A. Scata,Wenge Wang, all of Penn State Hershey Cancer Institute; Gabriel Krigsfeld, Patrick A. Mayes, Luv Patel, University of Pennsylvania School of Medicine; Evangelos Messaris, Department of Surgery, Penn State College Medicine; Jun-Ying Zhou and Gen Sheng Wu, Wayne State University School of Medicine.

This study was funded by the American Cancer Society, Penn State Hershey Cancer Institute and the National Institutes of Health.

Penn State

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

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.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.