IADR Abstract Archives
Deciphering HNSCC Intra Tumor Heterogeneity, an Approach Towards Personalized Medicine.
Objectives: Head and Neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide with 5-year survival rate of 40-50%. Therapies, including immune modulating treatments, radiotherapy and surgery, are common in treating advanced stages, but have shown no significant responses. One of the main reasons is inter and intra tumor heterogeneities which lead to treatment resistance.
Our goal is to decipher HNSCC inter and intra-tumor heterogeneities within patient-derived tumors, using single cell Surprisal Analysis, and to identify evolving subpopulations post common clinical treatments . We aim to sensitize HNSCC tumors to these treatments by targeting central proteins of the expanded subpopulations.
Methods: To resolve cellular heterogeneity within HNSCC tumors, we developed an information-theoretic single-cell quantification strategy which computes a barcode for every tumor cell and reflects a set of ongoing processes in each cell. Barcodes, representing each subpopulation, are further used to assign targeted drug combinations for each tumor to enhance tumor response to therapy. We validate this concept using patient-derived oral cancer tissues which change intra-cellular phenotypes in response to radiotherapy (RT). We plan to examine whether the barcode-guided targeted cocktail will enhance the tumors responses to RT and will prevent regrowth of initially resistant tumors. We hypothesize that individualized targeted therapy will also improve immune response. We will examine this by using humanized mice injected with human peripheral blood mononuclear cells (PBMC's) from healthy/diseased donors.
Results: Preliminary results demonstrate a significant expansion of distinct subpopulations in response to RT, such as a subpopulation in which PDL-1 protein expand, and another subpopulation with the expansion of EGFR proteins, in certain patient-derived tissue. These results suggests that a tumor response to RT can be enhanced through simultaneous inhibition of those subpopulations. The experiments are underway in our laboratory to validate this hypothesis.
Conclusions: We suggest that an accurate resolution of HNSCC intra-tumor heterogeneity will allow us to provide an essential step towards the accurate design of targeted drug combinations to overcome tumor resistance, with a broad applicability in clinical use.
Our goal is to decipher HNSCC inter and intra-tumor heterogeneities within patient-derived tumors, using single cell Surprisal Analysis, and to identify evolving subpopulations post common clinical treatments . We aim to sensitize HNSCC tumors to these treatments by targeting central proteins of the expanded subpopulations.
Methods: To resolve cellular heterogeneity within HNSCC tumors, we developed an information-theoretic single-cell quantification strategy which computes a barcode for every tumor cell and reflects a set of ongoing processes in each cell. Barcodes, representing each subpopulation, are further used to assign targeted drug combinations for each tumor to enhance tumor response to therapy. We validate this concept using patient-derived oral cancer tissues which change intra-cellular phenotypes in response to radiotherapy (RT). We plan to examine whether the barcode-guided targeted cocktail will enhance the tumors responses to RT and will prevent regrowth of initially resistant tumors. We hypothesize that individualized targeted therapy will also improve immune response. We will examine this by using humanized mice injected with human peripheral blood mononuclear cells (PBMC's) from healthy/diseased donors.
Results: Preliminary results demonstrate a significant expansion of distinct subpopulations in response to RT, such as a subpopulation in which PDL-1 protein expand, and another subpopulation with the expansion of EGFR proteins, in certain patient-derived tissue. These results suggests that a tumor response to RT can be enhanced through simultaneous inhibition of those subpopulations. The experiments are underway in our laboratory to validate this hypothesis.
Conclusions: We suggest that an accurate resolution of HNSCC intra-tumor heterogeneity will allow us to provide an essential step towards the accurate design of targeted drug combinations to overcome tumor resistance, with a broad applicability in clinical use.