May is National Cancer Research Month. Qin Yan, PhD, professor of pathology, director, Center for Epigenetics and Biomarkers, pathology, co-leader, Genomics, Genetics and Epigenetics Research Program, Yale Cancer Center, and scientific co-director, Center for Breast Cancer, Yale Cancer Center, speaks about his work.

Can you tell me why your research is focused on cancer?

Cancer is the leading cause of death and has impacted many people around us. Emerging evidence showed that epigenetic aberrations are as important as genetic changes in cancer initiation and progression.

Can you briefly describe your current work?

My current work aims to elucidate the roles of epigenetic mechanisms that drive tumor initiation and progression and to translate our findings to the clinic. In particular, my group focuses on the epigenetic drivers of cancer metastasis and immune evasion in breast cancer and melanoma.

What achievements are you most proud of?

Dr. Yan points to two studies. The first was published in Nature in 2021.

We found that loss of histone methylase KDM5B induces the expression of retroelements and activates both cytosolic RNA and DNA sensing pathways to induce robust anti-tumor immunity, leading to tumor rejection. Ablation of KDM5B also enhances responses of poorly immunogenic melanoma tumors to anti PD-1 treatment significantly. This study opens new paths for the development of KDM5B-targeting therapies to enhance tumor immunogenicity and overcome immunotherapy resistance.

The second was published in Science Translational Medicine in 2022.

Using the archival tumor tissues in Yale Pathology, we profiled the transcriptomes of paired primary and metastatic breast tumors and found that distant metastases are more immune inert compared to matched primary tumors. We discovered multiple epigenetic regulators that drive cancer metastasis, including an acetyl-lysine reader CECR2. Pharmacological inhibition of CECR2 bromodomain impeded breast cancer metastasis. This study reveals that small molecule CECR2 inhibitors can be used to treat metastatic breast cancer.