Cancer Weakness Discovered: New Method Pushes Cancer Cells Into Remission

Artistic Rendering of Cancer Cells

The most successful targets for precision medicine can be found by using algorithms created by University of Michigan researchers. These algorithms successfully identify the weakest targets in ovarian cancer cells—genes these cells depend on to live in the human body.

Cancer cells delete DNA when they go to the dark side, so a team of doctors and engineers targeted the ‘backup plans’ that run essential cell functions.

Researchers at the University of Michigan and Indiana University have discovered a cancer weakness. They found that the way that tumor cells enable their uncontrolled growth is also a weakness that can be harnessed to treat cancer. 

Their machine-learning algorithm can identify backup genes that only tumor cells use, allowing drugs to precisely target cancer.

The researchers used mice to demonstrate their innovative precision medicine approach to treating ovarian cancer. Furthermore, the cellular behavior that reveals these vulnerabilities is common in most cancers, implying that the algorithms might generate superior treatment plans for a variety of cancers.

Abhinav Achreja, Ph.D., Research Fellow at the University of Michigan Biomedical Engineering and Deepak Nagrath, Ph.D. Associate Professor of Biomedical Engineering work on ovarian cancer cell research in the bio-engineering lab at the North Campus Research Center (NCRC). Credit: Marcin Szczepanski/Lead Multimedia Storyteller, University of Michigan College of Engineering

“This could revolutionize the precision medicine field because the drug targeting will only affect and kill cancer cells and spare the normal cells,” said Deepak Nagrath, a U-M associate professor of biomedical engineering and senior author of the study published in Nature Metabolism. “Most cancer drugs affect normal tissues and cells. However, our strategy allows specific targeting of cancer cells.”

This method is known as collateral lethality, and it involves leveraging information acquired from genes that cancer cells discard to identify weaknesses. The human body is equipped with a variety of defenses against cancer. Cancer cells used to have suppressor genes that prevented them from spreading. Those cells, however, have a clever strategy for dealing with this; they simply delete a portion of their DNA that contains those suppressor genes.

In doing so, the cells typically lose other genes that are necessary for survival. To avoid death, the cells find a paralog—a gene that can serve a similar function. Usually, there are one or, possibly, two genes that can step in and perform the same function to keep the cell alive.

What if you could identify the right paralog and target it in a way that shuts down its vital function for the cell?

“When a direct replacement for the deleted metabolic gene is not available, our algorithms use a mathematical model of the cancer cells’ metabolism to predict the paralogous metabolic pathway they might use,” said Abhinav Achreja, a U-M research fellow in biomedical engineering and lead author on the research paper. “These metabolic pathways are important to the cancer cells and can be targeted selectively.”

Attacking metabolic pathways essentially shuts down the cell’s energy source. In examining ovarian cancer cells, U-M’s team zeroed in on one gene, UQCR11, that was often deleted along with a suppressor gene. UQCR11 plays a vital role in cell respiration—how cells break down glucose for energy in order to survive.

Disturbances in this process can lead to a major imbalance of an important metabolite, NAD+, in the mitochondria, where respiration takes place. Despite all odds, ovarian cancer cells continue to thrive by relying on their backup plan.

U-M’s algorithm correctly sorted through multiple options and successfully predicted a cell missing UQCR11 would turn to the gene MTHFD2 as its backup supplier of NAD+.

Researchers at the Indiana University School of Medicine helped validate the findings in the lab. This team, led by professor of medicine Xiongbin Lu, developed genetically modified cell and animal models of ovarian cancers with the deletions. Six out of six mice tested showed complete cancer remission.

Reference: “Metabolic collateral lethal target identification reveals MTHFD2 paralogue dependency in ovarian cancer” by Abhinav Achreja, Tao Yu, Anjali Mittal, Srinadh Choppara, Olamide Animasahun, Minal Nenwani, Fulei Wuchu, Noah Meurs, Aradhana Mohan, Jin Heon Jeon, Itisam Sarangi, Anusha Jayaraman, Sarah Owen, Reva Kulkarni, Michele Cusato, Frank Weinberg, Hye Kyong Kweon, Chitra Subramanian, Max S. Wicha, Sofia D. Merajver, Sunitha Nagrath, Kathleen R. Cho, Analisa DiFeo, Xiongbin Lu and Deepak Nagrath, 21 September 2022, Nature Metabolism.
DOI: 10.1038/s42255-022-00636-3

The study was funded by the National Cancer Institute, the Office of the Director for the National Institutes of Health, the University of Michigan Precision Health Scholars Award, and the Forbes Scholar Award from the Forbes Institute of Cancer Discovery.


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  • This is great stuff until Big Pharma waves a fat check in front of their faces wanting to buy the rights to the discovery. Once Big Pharma get the rights, they will shelve this discovery so they can continue to push their failed "chemo" treatment. Remember, it's always more profitable to "treat" than to CURE. For over 20 years we've been hearing of these cancer "breakthroughs", but where are they now? If you think for one second Big Pharma will ever allow cures for cancer, I have a bridge I can sell you ;-). Merry Christmas!

      • Absolutely. If they can't buy him, they will bog it down in the FDA approval process, whereas they quickly greenlighted another highly experimental gene therapy for a disease with 99+% survivability and mandated that all humanity take it before it has even been animal tested.

  • Blessings to those who keep persisting in this admirable work. Don't stop your efforts. Cancer patients need you!

  • Likely too late a brilliant discovery for me as my cancer is in my sinuses, extremely aggressive and this promising approach will hopefully benefit many in the near future! Praying for them and myself. F*** Cancer!!!

  • Keep fighting this war,for us. Cancer will be defeated with these great young people who I love and thanks formore time.James Cancer in Columbus.

  • I’m definitely concern about Big Pharm. Let get this product through. We need the help. Thank all that worked so hard on this Progress. Go is Stronger than us all.I keep 🙏 praying

  • This is such great news. Thank you for all of your hard work and time spent on all of your fact finding and trial testing. As a cancer survivor what we fear most is cancer coming back. Staying in remission is key. Again thank you for all of your time and energy that you put into this. Huge WIN!

  • I would love to be in the clinical trial. A targeted chemotherapy is now keeping me alive, but my cancer is likely to find a way around it eventually.

  • Love all the efforts all the scientists are exploring to help us the cancer patients but like Gerry said big pharm is in control of those looking for a cure and will not allow or will disregard all their efforts. The only people that can back them up are the patients on chemo and amatase inhibitors refuse to take these meds. They create more damage to the rest of normal cells destroying the patients in a slow methodical method and creating new damage, ( brain, cognitive damage permanent, destruction of nerves system, called neuropathy. Which can kill you after reaching stage 5. Muscle damage performance leading to permanent damage and personally putting you in a wheelchair ect) but big pharm really is not there to cure only greed to recieve the 4,000.00 dollars ever 28 days for each chemo they give for long term chemo like bone cancer 1. Year. Lymphoma 1 year of treatment breast cancer depending on stage between 6 months to up to over 10 cycles. Which is 10 months. Or more Etc...
    This does not include the isolation of a patients long term to stay away from groups. Unable to enjoy simple things like go to a therater enjoying a movie. Family members not visiting afraid they will make you sick because your immunity is low etc..No big pharmand the FDA does not care. Money rules not human life, if cured, you can achieve once again to become an active member of society again. Paying taxes. Contributing

    • I am curious about your comment please email me if you would.
      Thank you in advance,
      Dec 2nd 1990

  • I agree with the previous comment. In the United States especially big pharma will never let a cure reach anyone. More money is made on the sick than people getting better. Big pharma will always run the show .

  • This whole cancer field is sick itself. Yes on big pharma and how they work. Know one young was told if she raised $500 million MAYBE they would try to study her cancer. She did, they named a new room in clinic after her, and her grave is not far from here. Sick, sick programs, pharma $$$$ biggest gain, not patients.

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