New algorithm detects even the smallest cancer metastases across the entire mous

December 12, 2019

Cancer is one of the leading causes of death worldwide. More than 90% of cancer patients die of distal metastases rather than as a direct result of the primary tumor. Cancer metastases usually develop from single disseminated cancer cells, which evade the body's immune surveillance system. Up to now, comprehensive detection of these cells within the entire body has not been possible, owing to the limited resolution of imaging techniques such as bioluminescence and MRI. This has resulted in a relative lack of knowledge of the specific dissemination mechanisms of diverse cancer types, which is a prerequisite for effective therapy. It has also hampered efforts to assess the efficacy of new drug candidates for tumor therapy.

Transcending human detection capabilities with deep learning

In order to develop new techniques to overcome these hurdles, the team led by Dr. Ali Ertürk, Director of the Institute for Tissue Engineering and Regenerative Medicine at Helmholtz Zentrum München, had previously developed vDISCO - a method of tissue clearing and fixation which transforms mouse bodies into a transparent state allowing the imaging of single cells. Using laser-scanning microscopes, the researchers were able to detect the smallest metastases down to individual cancer cells in cleared the tissue of the mouse bodies.

However, manually analyzing such high-resolution imaging data would be a very time-consuming process. Given the limited reliability and processing speed of currently available algorithms for this kind of data analysis, the teams have developed a novel deep-learning based algorithm called DeepMACT. The researchers have now been able to detect and analyze cancer metastases and map the distribution of therapeutic antibodies in vDISCO preparations automatically. The DeepMACT algorithm matched the performance of human experts in detecting the metastases - but did so more than 300 times faster. "With a few clicks only, DeepMACT can do the manual detection work of months in less than an hour. We are now able to conduct high-throughput metastasis analysis down to single disseminated tumor cells as a daily routine", says Oliver Schoppe, co-first-author of the study and Ph.D. student in the group of Prof. Dr. Bjoern Menze at TranslaTUM, the Center for Translational Cancer Research at TUM.

Detecting cells, gathering data, learning about cancer

Using DeepMACT, the researchers have gained new insights into the unique metastatic profiles of different tumor models. Characterization of the dissemination patterns of diverse cancer types could enable tailored drug targeting for different metastatic cancers. By analyzing the progression of breast-cancer metastases in mice, DeepMACT has uncovered a substantial increase in small metastases throughout the mouse body over time. "None of these features could be detected by conventional bioluminescence imaging before. DeepMACT is the first method to enable the quantitative analysis of metastatic process at a full-body scale", adds Dr. Chenchen Pan, a postdoctoral fellow at Helmholtz Zentrum München and also joint first author of the study. "Our method also allows us to analyze the targeting of tumor antibody therapies in more detail."

How effective are current cancer therapies?

With DeepMACT, the researchers now have a tool with which to assess the targeting of clinical cancer therapies that employ tumor-specific monoclonal antibodies. As a representative example, they have used DeepMACT to quantify the efficacy of a therapeutic antibody named 6A10, which had been shown to reduce tumor growth. The results demonstrated that 6A10 can miss up to 23% of the metastases in the bodies of affected mice. This underlines the importance of the analysis of targeting efficacy at the level of single metastases for the development of novel tumor drugs. The method can potentially also track the distribution of small-molecule drugs when they are conjugated to fluorescent dyes.

On the way to stop the metastatic process

Taken together, these results show that DeepMACT not only provides a powerful method for the comprehensive analysis of cancer metastases, but also provides a sensitive tool for therapeutic drug assessment in pre-clinical studies. "The battle against cancer has been underway for decades and there is still a long way to go before we can finally defeat the disease. In order to develop more effective cancer therapies, it is critical to understand the metastatic mechanisms in diverse cancer types and to develop tumor-specific drugs that are capable to stop the metastatic process," explains Ertürk.

DeepMACT is publicly available and can be easily adopted in other laboratories focusing on diverse tumor models and treatment options. "Today, the success rate of clinical trials in oncology is around 5%. We believe that the DeepMACT technology can substantially improve the drug development process in preclinical research. Thus, could help finding much more powerful drug candidates for clinical trials and hopefully help to save many lives".
-end-
Watch the video to learn more about DeepMACT: https://vimeo.com/374124521

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,500 staff members. It is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

Helmholtz Zentrum München - German Research Center for Environmental Health

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.