Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer

We have developed a next-generation sequencing assay to quantify biomarkers of the host immune response in formalin-fixed, paraffin-embedded (FFPE) tumor specimens. This assay aims to provide clinicians with a comprehensive characterization of the immunologic tumor microenvironment as a guide for therapeutic decisions on patients with solid tumors. The assay relies on RNA-sequencing (seq) to semiquantitatively measure the levels of 43 transcripts related to anticancer immune responses and 11 transcripts that reflect the relative abundance of tumor-infiltrating lymphocytes, as well as on DNA-seq to estimate mutational burden. The assay has a clinically relevant 5-day turnaround time and can be conducted on as little as 2.5 ng of RNA and 1.8 ng of genomic DNA extracted from three to five standard FFPE sections. The standardized next-generation sequencing workflow produced sequencing reads adequate for clinical testing of matched RNA and DNA from several samples in a single run. Assay performance for gene-specific sensitivity, linearity, dynamic range, and detection threshold was estimated across a wide range of actual and artificial FFPE samples selected or generated to address preanalytical variability linked to specimen features (eg, tumor-infiltrating lymphocyte abundance, percentage of necrosis), and analytical variability linked to assay features (eg, batch size, run, day, operator). Analytical precision studies demonstrated that the assay is highly reproducible and accurate compared with established orthogonal approaches.

Decoding the HRD puzzle: The key to precision oncology in ovarian cancer

In the evolving landscape of ovarian cancer treatment, homologous recombination deficiency (HRD) testing plays a vital role in guiding personalized care. Although HRD testing has the potential to inform maintenance therapy selection, real-world data demonstrate that it remains underutilized-resulting in many patients never being assessed for potential eligibility for targeted therapy. Expanding the use of HRD testing could significantly enhance outcomes for patients with epithelial ovarian, fallopian tube, and primary peritoneal cancers. HRD refers to a tumor’s inability to effectively repair double-stranded DNA breaks through the homologous recombination repair (HRR) pathway. When HRR is compromised, tumor cells rely on alternative, error-prone repair mechanisms, leading to genomic instability—a hallmark of cancer. Approximately 50% of advanced ovarian cancer cases exhibit HRD, making it a critical biomarker for selection of maintenance therapies. 

NIH:OVCAR-3 human ovarian cancer model

Ovarian cancer, a formidable gynecological malignancy, poses a significant threat to women's health worldwide.1 Its nature often leads to late-stage diagnosis, contributing to poor prognosis and limited treatment options. To unravel the complexities of this disease and pave the way for effective therapeutic strategies, extensivein vitro and in vivo research is crucial. The NIH:OVCAR-3 cell line stands out as a widely utilized and well-characterized model in this research.2