USE OF CANCER CELL EXPRESSION OF CADHERIN 12 AND CADHERIN 18 TO TREAT MUSCLE INVASIVE AND METASTATIC BLADDER CANCERS

Smart overview of the Invention

Research has identified specific cancer cell populations in muscle-invasive bladder cancer (MIBC) that express Cadherin 12 (CDH12) and Cadherin 18, which are linked to treatment responses. The study utilized advanced techniques like single nuclei RNA sequencing and spatial transcriptomics to analyze human bladder cancer, revealing that CDH12-enriched tumors are associated with poorer outcomes after surgery and chemotherapy but show better responses to immune checkpoint therapy.

Importance of Patient Stratification

Stratifying patients based on CDH12 expression levels in tumors provides a more accurate prediction of treatment outcomes compared to existing bladder cancer subtypes. The presence of CDH12 is indicative of a more undifferentiated state, which contributes to chemoresistance and is associated with immune evasion mechanisms, such as the expression of PD-L1 and PD-L2.

Detection Methods for Tumor Phenotypes

Methods have been developed to detect various gene expression patterns in tumor cells, which help classify cancer samples and guide prognosis or treatment selection. These methods can distinguish between CDH12-high and CDH12-low phenotypes, as well as identify other relevant gene expressions associated with different tumor characteristics, enhancing the understanding of tumor biology.

Prognostic Implications for Treatment Selection

The detection of specific phenotypes can inform treatment strategies. For instance, a CDH12-high phenotype suggests sensitivity to immunotherapy, while a CDH12-low phenotype indicates a potential response to chemotherapy. This stratification allows for personalized treatment approaches, improving patient outcomes based on their tumor biology.

Applications in Cancer Treatment

The methodologies outlined can be applied to various cancers, particularly bladder cancer and its subtypes. By leveraging gene expression patterns and mutations, clinicians can make informed decisions regarding treatment options, ultimately aiming to enhance therapeutic efficacy and patient survival rates through tailored approaches.