Targeting “Zombie” Cells Offers New Hope for Pancreatic Cancer Treatment
NIH grant funds TGen research on senescent cells in pancreatic cancer therapy
A $493,680 NIH grant awarded to TGen, part of City of Hope, supports a promising new approach to treating pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers with a five-year survival rate of just 13 percent. The grant-funded research focuses on targeting and eliminating “zombie” cells—damaged, dysfunctional cells that contribute to tumor growth and immune suppression, providing a significant opportunity to advance treatment options for this challenging cancer.
“Senescent cells, or ‘zombie’ cells, remain active in the tumor environment despite being damaged,” said Haiyong Han, Ph.D., a professor in the Clinical Genomics and Therapeutics Division at TGen and the study’s principal investigator. “These cells release signals that promote inflammation and tumor progression. By targeting and removing these cells, we believe we can alter the tumor microenvironment, making it more responsive to treatment.”
The study will explore the effects of SIWA318, a novel therapeutic antibody designed to target senescent cells in pancreatic cancer. Preliminary results from preclinical models show promise, with SIWA318 helping to reduce tumor growth and enhance immune responses in the tumor environment.
“The goal is to develop a therapy that not only targets the cancer cells but also reprograms the tumor microenvironment to support better responses to existing treatments,” said Han.
Han and his colleagues will use advanced PDAC mouse models, including a humanized patient-derived xenograft (PDX) model and the KPC transgenic mouse model. These models will allow the researchers to investigate how targeting senescent cells impacts tumor growth and treatment outcomes.
PDAC is the third leading cause of cancer-related deaths in the United States. Despite ongoing research, the disease remains highly resistant to most treatments, with a median survival rate of 9-11 months for patients with advanced stages. If successful, this approach could significantly improve treatment options for PDAC patients, who currently face limited survival rates and few effective therapies.
The findings may also have broader implications for other cancers and age-related diseases. The work builds on an earlier study results published in the Nature journal Scientific Reports by Han and colleagues in a 2023 paper entitled Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer.
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