New model mimics human tumors for accurate testing of cancer drugs

October 11, 2018

Walter and Eliza Hall Institute researchers have genetically engineered a new laboratory model that enables accurate testing of anti-cancer drugs by mimicking the complexity of human cancers.

Using this advanced model, researchers will be able to discover the safest and most effective ways to use promising drugs called MCL-1 inhibitors in the clinic.

The work was led by PhD student Ms Margs Brennan, Dr Gemma Kelly and Associate Professor Marco Herold, and has been published in the journal Blood.

At a glance

Attacking cancer's Achilles' heel

MCL-1 is a protein essential for the sustained growth of many blood cancers, as well as some solid tumours including breast cancer and melanoma. Dr Kelly said this role in promoting cancer cell survival makes MCL-1 an attractive therapeutic target.

"MCL-1 allows cancer cells to evade the process of programmed cell death, or apoptosis, that normally removes damaged or unwanted cells from the body.

"Because so many cancer cells depend on MCL-1 for survival, it is like cancer's Achilles' heel - if we can attack this weak point with a drug, we may be able to successfully trigger apoptosis and destroy cancer cells for good," Dr Kelly said.

A highly potent inhibitor of MCL-1, called S63845, has been developed by pharmaceutical company Servier. While the drug is known to trigger cancer cell death in the laboratory, until now there was no accurate tool to predict how the drug would work in patients.

Rigorous testing for targeted clinical use

In this new study, researchers genetically engineered a model to accurately evaluate MCL-1 inhibitors. The model is the best available for laboratory-based studies evaluating S63845, closely predicting how cancer patients will respond to the drug in the clinic.

Ms Brennan said the laboratory model will allow researchers to find the best ways to match MCL-1 inhibitors with the right cancer patients.

"Using this model, we can get a handle on key questions such as which types of cancers are sensitive to MCL-1 inhibitors, which patients will benefit, which combination treatments will be most effective and the best dosing regimens to use.

"Working with laboratory models that closely mimic human cancer allows us to gain as much knowledge about MCL-1 inhibitors as we can before the drugs even reach the clinic. This lays the groundwork for future clinical trials, hopefully improving treatment options for patients," she said.

Powerful potential for treatments

To demonstrate the potential of this new research tool, the researchers used it to test whether MCL-1 inhibitors could effectively treat a preclinical model of lymphoma.

"We found that treatment with the MCL-1 inhibitor S63845 led to remission in six out of 10 cases of lymphoma," Associate Professor Herold said. "This was achieved without significant side effects, suggesting that S63845 will be safe and effective in the clinic."

Associate Professor Herold said MCL-1 inhibitors could be particularly powerful when combined with standard treatments like chemotherapy.

"MCL-1 allows cancer cells to resist treatments like chemotherapy that would otherwise trigger cell death. In our preclinical model, we found that combining an MCL-1 inhibitor with chemotherapy led to remission in almost all cases of lymphoma," he said.

The team is now using their laboratory model to test whether MCL-1 inhibitors are effective for other types of blood cancers. They will also share the model with other members of the scientific community studying MCL-1 inhibitors in different disease contexts.

"Our laboratory model will be invaluable for future preclinical work determining the best uses of MCL-1 inhibitors for treating human disease," Associate Professor Herold said.
-end-
This work was supported by the Australian National Health and Medical Research Council, Servier Laboratories, the Leukemia and Lymphoma Society of America, the Cancer Council of Victoria, the Victorian Cancer Agency, the Leukaemia Foundation, the Estate of Anthony (Toni) William Redstone OAM, the Craig Perkins Cancer Research Foundation, Mr Malcolm Broomhead, the Australian Government and the Victorian State Government.

Walter and Eliza Hall Institute

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.