Sichun Yang, PhD, a member of Case CCC's Molecular Oncology Program, and Alberto Montero, MD, a Developmental Therapeutics Program member, are looking for patient advocates for a follow-up study to Yang's recent structure-function study, The sequence-structure-function relationship of intrinsic ERα disorder (Nature 2025; PMID 39779860).
This study revealed that pSer118 functions as a molecular switch in estrogen receptor's (ER) intrinsically disordered regions, fundamentally altering receptor conformational dynamics, enabling estrogen-independent activation, and creating an exceptionally high baseline ER expression in invasive lobular breast cancer (ILC).
Given these findings, Yang proposed that phosphorylation-driven signaling may disproportionately influence disease progression and treatment resistance in this subtype.
Although phosphorylation of ER at serine 118 (pSer118) enables estrogen-independent signaling in breast cancer broadly, Yang and Montero point out that its specific contribution to metastatic progression in ILC is largely unexplored. Thus, the researchers launched a unique approach to study breast cancer subtype ILC—a condition in which over 90% of cases express significantly higher levels of estrogen receptor (ER) compared with invasive ductal carcinoma.
If you have current patients who have this type of cancer and are interested in informing this new study, please refer them to Sichun Yang, sichun.yang@case.edu.