OUR RESEARCH
How does intratumoral heterogeneity impact molecular subtypes and biomarker risk stratification?
Molecular subtypes have historically been classified using bulk RNA sequencing studies, which evaluate gene expression across an entire tumor sample, without taking into account the types of tumor, immune, and stromal cells present.
However, recent studies have demonstrated that spatially distinct areas of one tumor may have differing cellular composition or tumor cells with different molecular alterations, a concept known as intratumoral heterogeneity. This heterogeneity may result in different molecular biomarker classifications for two spatially distinct areas of one tumor.
The Gessner Lab is exploring how this intratumoral heterogeneity impacts the use of molecular biomarker classifications and risk stratification, as well as the plasticity of molecular subtypes of genitourinary malignancies.
How do different histologic subtypes promote changes in the tumor microenvironment and therapeutic resistance?
Different histologic subtypes of cancer can influence the composition of the tumor microenvironment, resulting in therapeutic resistance. One possible mechanism is that molecular alterations or mutations unique to the variant histology may recruit or activate immune or stromal cells differently compared to the more common histology.
By studying histologic subtypes, which inherently have a high level of intratumoral heterogeneity, we are working to understand mechanisms of cross-talk between cancer cells and other cell types in the tumor which contribute to therapeutic resistance. Our goal is to ultimately utilize what we learn about tumor-immune or tumor-stromal cell cross-talk to identify more effective therapies.
How can we exploit intratumoral heterogeneity to develop more effective therapies?
While it is widely accepted that intratumoral heterogeneity exists, it is not well understood how we can exploit it to more effectively treat cancer. Our goal is to utilize what we learn about the complexities of intratumoral heterogeneity, both at the level of tumor cells and the tumor microenvironment, to develop more effective therapies.
To achieve this goal, we are utilizing a combination of human samples, patient-derived organoids, and cell lines to develop new preclinical model systems and improve treatment options for patients.
