59 Biological sex influences cancer in ways that can affect how the disease develops and responds to treatment. In lung cancer, squamous cell carcinoma disproportionately affects males, while adenocarcinoma occurs more frequently in females. Researchers are investigating the cellular mechanisms behind these divergent outcomes across lung and other cancers to improve care for physicians and patients. Scientists at Sanford Burnham Prebys Medical Discovery Institute published findings on 15th July 2026 in BMJ Oncology. The study demonstrates differences in protein levels in tumour samples from male and female patients. Lung cancer showed more sex-based protein differences than other cancer types with available data. The authors also emphasised the need for more protein sequencing of clinical tumour samples to support further research. Following the Human Genome Project, the National Institutes of Health launched The Cancer Genome Atlas programme in 2006. It sequenced the genomes and gene expression of tens of thousands of cancer samples across 33 cancer types. Five years later, the Clinical Proteomic Tumour Analysis Consortium (CPTAC) was established to link genetic sequences, gene expression patterns, and proteins in tumours. “This was very important for the field,” said Chenghao (Trevor) Zhu, PhD, a research assistant professor at the NCI-designated Cancer Center at Sanford Burnham Prebys. “While we had earlier access to clinical genomics information, there weren’t any public resources allowing us to answer the questions we had about the cancer proteome until CPTAC began releasing data.” The research team analysed protein sequencing data from 934 cancer patients across eight cancer types for sex-based differences. They began by examining normal cells adjacent to tumours. “We know that tumours are derived from normal cells,”said Paul Boutros, PhD, MBA, of Sanford Burnham Prebys. “That means we need to define the proteins in what is called tumour-adjacent normal tissue to serve as controls for comparing to the proteins in tumour cells.” These comparisons showed that lung adenocarcinoma had the most sex-based differences, with 901 proteins found in varying abundance between male and female patient samples Lung adenocarcinoma stood out for its strong sex-based differences in protein levels. “The other lung cancer type we studied, squamous cell carcinoma, had more modest changes,” said Zhu, the lead and co-corresponding author of the study. Along with lung squamous cell carcinoma, the team observed moderate sex-based differences in kidney renal clear cell carcinoma, pancreatic ductal adenocarcinoma, liver hepatocellular carcinoma, and glioblastoma. No significant differences appeared in colon adenocarcinoma or head and neck squamous cell carcinoma. To determine whether the proteomic differences related to key cancer cell functions, the scientists used data from the Dependency Map Consortium. This initiative accelerates precision cancer medicine by identifying genes required for cell growth in various cancers. They cross-referenced genes with sex differential protein abundance in lung adenocarcinoma against findings from 52 lung adenocarcinoma cell lines. “When the genes we had identified were knocked out with CRISPR gene editing, it led to worse survival in the cell lines,” said Zhu. The proteomics study builds on prior groundbreaking research into sex-based differences in cancer genomics. Constance H. Li, PhD, assistant professor at the University of Calgary and former Boutros lab member, led the early studies. These revealed differences in mutation density and mutation frequency of specific genes, including major cancer drivers. One study identified sex-biased differences across 1,983 tumour samples and 28 tumour subtypes. The team plans to expand proteomics research by analysing newer CPTAC data and ongoing treatment response studies. These will examine proteomic changes linked to treatment resistance and cancer recurrence. Proteins play a central role in cancer biology, and they are the most common drug targets and biomarkers. “Better understanding the cancer proteome and what shapes it is key to treating patients more precisely based on their unique characteristics and those of their cancers,” said Boutros, the senior and co-corresponding author of the manuscript. With proteins serving as primary drug targets, the findings may inform future precision medicine strategies that account for patient sex.