In a new study from the University of Toronto, researchers found that about half of patient-derived pancreatic cancer cell lines are highly dependent or “addicted” to the protein peroxiredoxin 4 (PRDX4), as a result of the altered metabolic state of the cancer cell.
This addiction is vital for the cancer cell’s survival, thereby also making it a precise, potential target against cancer.
Pancreatic cancer is a deadly disease with overall five-year survival of only eight percent.
Moreover, 36% to 46% of patients who undergo surgery with curative intent develop a recurrence of pancreatic cancer, despite adjuvant chemotherapy.
It’s been known for decades that cancer cells acquire key changes in their metabolism to support their continuous need for building blocks from nutrients to divide and grow faster.
In the study, the team found that the same metabolic deregulation that fuels cell growth can create novel vulnerabilities in cancer.
It was previously known that pancreatic cancer cells increased levels of a key metabolite known as NADPH which acts to fuel uncontrolled levels of cell growth.
The researchers discovered that high levels of NADPH in the pancreatic cancer cells created a novel form of oxidative stress and a corresponding requirement for PRDX4 to survive.
Essentially, cancer cells need PRDX4, an antioxidant protein, to destroy the toxic byproducts resulting from uncontrolled metabolism.
The team showed that targeting PRDX4 in patient-derived cancer cells lines led to toxic accumulation of oxidative stress, resulting in DNA damage, and cell death, and impaired tumor growth in preclinical models.
Equally important, loss of PRDX4 had no measurable effect on normal cells.
Taken together, this study reveals the potential of targeted therapies to exploit unique metabolic features of cancer cells that are far more specific than, for example, chemotherapy which affects both cancer and normal cells.
If you care about pancreatic cancer, please read studies about a new treatment for pancreatic cancer and findings of this tongue test may help detect pancreatic cancer early.
For more information about pancreatic cancer prevention and treatment, please see recent studies about three simple ways to cut the risk of pancreatic cancer and results showing that this common health condition may increase pancreatic cancer risk.
The study is published in Science Advances. One author of the study is Dr. Marianne Koritzinsky.
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