Chemosensitivity Mediator and Immunotherapy Target Identified in Ovarian Cancer
Posted: Thursday, December 13, 2018
A study published in the journal Cell found that using clinical cancer proteomics in clinical tumor samples to identify targets for chemotherapy and immunotherapy may prove valuable in the treatment of patients with high-grade ovarian cancer. Fabian Coscia, PhD, of the University of Copenhagen, Denmark, and colleagues identified that cancer/testis antigen 45 (CT45) seems to enhance chemosensitivity in metastatic ovarian cancer and suggested it may prove to be a factor in the long-term survival of this patient population.
“This study highlights the power of clinical cancer proteomics to identify targets for chemo- and immunotherapy and illuminate their biological roles,” the investigators commented.
The researchers analyzed the proteomes of platinum-resistant and platinum-sensitive patients with high-grade serous ovarian cancer from formalin-fixed, paraffin-embedded tumors. They found CT45 to be an independent prognostic factor associated with a doubling of disease-free survival in advanced-stage high-grade serous ovarian cancer. The discovery cohort focused on 3 patients with CT45-positive tumors, showing relapse-free long-term survival for an average of 7 years.
“Phospho- and interaction proteomics linked CT45 to DNA damage pathways through direct interaction with the PP4 phosphatase complex,” explained Dr. Coscia’s team. “In vitro, CT45 controlled PP4 activity, and its high expression led to increased DNA damage and platinum sensitivity.”
In future studies, researchers may attempt to identify the T-cell receptor responsible for recognition of CT45. Then, they may also engineer T cells recognizing CT45 for adoptive T-cell transfer in the setting of acquired platinum resistance. Currently in clinical trials is another possible treatment strategy for patients who lack CT45, which attempts to reactivate CT45 expression with demethylating agents.