Researchers Uncover New Insights into Cancer Mortality Causes

A groundbreaking study led by researchers at UT Southwestern Medical Center suggests that the primary cause of cancer-related deaths may not stem from metastatic disease, as previously believed. Instead, the research indicates that tumors infiltrating major blood vessels can lead to blood clots and subsequent multiorgan failure. These findings, published in the journal Nature Medicine on October 16, 2025, could pave the way for new treatment strategies aimed at prolonging the lives of patients with advanced cancers.

Dr. Matteo Ligorio, an Assistant Professor of Surgery at UT Southwestern, spearheaded the study alongside Dr. Kelley Newcomer, an Associate Professor of Internal Medicine, and Dr. Nicola Aceto, a Professor of Molecular Oncology at ETH Zurich in Switzerland. “The main question we sought to address was: What kills cancer patients, and why do they pass away on a specific day rather than months earlier or later?” Dr. Ligorio explained.

Cancer is responsible for approximately 600,000 deaths annually in the United States. Despite this alarming statistic, the mechanisms behind these fatalities have remained obscure. Previous research suggested that the spread of cancer, known as metastasis, was the primary culprit. Yet, many patients manage to live with metastatic disease for years, indicating that other factors contribute to their decline.

The study involved a retrospective analysis of over 100 patients diagnosed with colorectal, lung, ovarian, liver, or pancreatic cancer who had died at William P. Clements Jr. University Hospital and Parkland Health. Dr. Newcomer also recruited 31 terminally ill patients in hospice care, monitoring their health status and collecting blood samples during significant health changes.

Upon the patients’ passing—an average of approximately 38 days after enrollment—Dr. Ligorio performed modified autopsies. Unlike conventional practices, this method preserved the integrity of major blood vessels, allowing for detailed examination. The results revealed that cancer patients frequently had tumors penetrating the walls of significant blood vessels, including the portal vein and inferior vena cava.

In several cases, CT scans indicated the presence of these invasive tumors weeks or months before death, suggesting they may be detectable through standard imaging techniques. Blood samples analyzed by Dr. Aceto’s team at ETH Zurich showed a notable increase in cancer cells in the bloodstream just prior to death, highlighting the cardiovascular system’s significant role in disease progression.

Based on these observations, Dr. Ligorio proposed a new hypothesis regarding cancer fatalities. He theorized that when tumors invade major blood vessels, fragments may detach and enter the bloodstream, increasing the likelihood of clot formation. These clots can obstruct blood flow to vital organs, ultimately leading to multiorgan failure and death.

To further validate this hypothesis, the research team examined CT imaging data from 1,250 cancer patients who had died. Collaborators from the University of Lubeck and the University of Mainz in Germany confirmed that a majority of these patients had tumors infiltrating significant blood vessels, reinforcing the new understanding of cancer progression.

Dr. Newcomer pointed out that this research could transform cancer treatment strategies. “Surgery or radiation targeting tumors near large blood vessels could reshape how we diagnose, manage, and treat cancer patients,” she stated.

The researchers expressed gratitude to the patients and their families who participated in the study. They also acknowledged the collaboration of three hospice organizations: Visiting Nurse Association of Texas, Faith Presbyterian Hospice, and Pathway Hospice.

Looking ahead, Drs. Ligorio and Newcomer are working with Dr. Herbert J. Zeh III, Chair and Professor of Surgery at UT Southwestern, to design clinical trials that will test these new therapeutic approaches. The goal is to determine whether directly targeting tumor-vessel infiltration can significantly extend survival, particularly in patients with advanced disease.

This study received funding from various organizations, including the Cancer Prevention and Research Institute of Texas, the National Cancer Institute, and the Swiss National Science Foundation, among others. A complete list of contributors and their disclosures is available in the published study.

UT Southwestern Medical Center remains a leading academic institution known for its integration of cutting-edge biomedical research and exceptional clinical care, contributing to significant advancements in medical science and patient care.