New Database Documents Sex Differences in Cancer Biology, Risk Factors, and Treatments

A groundbreaking new database could lead to vast improvements in precision oncology by documenting sex-based differences in cancer treatment efficacy, biomarkers, risk factors, and microbial influences across 71 cancer types. The database — created by researchers at the Yale School of Public Health (YSPH), Yale School of Medicine (YSM), and international collaborators — addresses a significant gap in current research and demonstrates how biological sex can comprehensively impact cancer onset, progression, and therapeutic outcomes, the researchers said.

The project, which the researchers call OncoSexome, was created in response to the tendency of scientists and clinicians to overlook sex differences in clinical trials.

“It’s concerning that most cancer clinical trials historically overlooked sex differences,” said Xinyi Shen, MPH '21, a YSPH doctoral student and one of the lead authors of a paper on the database published in Nucleic Acids Research. Shen explained that one major feature of OncoSexome reveals how “cancer drugs exhibit significantly different effects in males versus females” in therapeutic efficacy and adverse responses​.

A National Cancer Institute study published earlier this year found that although only 0.5% of oncology clinical trials had curated post-treatment sex comparisons, many of these trials uncovered important differences in treatment outcomes. These findings highlight the critical importance of considering sex differences when planning treatment strategies, the Yale researchers said. For example, females receiving adjuvant fluoropyrimidine-based chemotherapy for colon cancer experienced higher toxicity rates.

OncoSexome implements a 2016 NIH policy that mandates the inclusion of sex as a biological variable in research proposals, a requirement that has shed light on the importance of understanding sex-based disparities.

“After constructing such a database, we are able to collect evidence supporting that certain drugs should be prescribed differently for males and females,” said Shen. She emphasized that the goal is to avoid a “one-size-fits-all” approach to cancer care, encouraging treatments tailored to each sex’s unique biological response.

OncoSexome is the first comprehensive cancer database to capture sex-based differences across four interconnected domains: drug responses, biomarkers, cancer risk factors, and microbiome variations. It catalogs sex-based information on 2,051 anticancer drugs, 12,551 oncological biomarkers, 350 cancer risk factors, and 1,386 microbes. The evidence-based approaches combine diverse data sources with rigorous cross-referencing for validation. The database will keep evolving as new data emerges.

The interactive, user-friendly interface of the online database makes it an essential tool for translating sex-differentiated data into actionable insights that transform future advances in sex-aware cancer research and clinical practice.

Caroline Helen Johnson, an associate professor of epidemiology (environmental health sciences) at YSPH and OncoSexome’s co-creator, noted how the database is unprecedented.

“Having information on both internal and external contributors to cancer, such as environmental chemicals or the microbiome, in one place is really beneficial,” said Johnson, who is also a member of Yale Cancer Center. “It’s just a resource for everyone.”

Johnson added that she hopes the database will raise awareness among researchers and clinicians “that there are differences between individuals in risk factors, biomarkers, and how we respond to drugs.”​

Other authors of the study include Dr. Andrew Thomas DeWan and Ms. Yechi Zhang from YSPH, Dr. Samuel David Butensky and Dr. Sajid A Khan from YSM, Dr. Feng Zhu, Dr. Yintao Zhang and Dr. Ying Zhou from Zhejiang University, Dr. Hong Yan, Dr. Zongwei Cai and Ms. Jiamin Li from Hong Kong Baptist University.