The major reason for caner relapse is the development of resistance to therapy. Our lab is dedicated to understand, and overcome, the primary mechanism(s) of cancer resistance.
Metastasis is the leading cause of cancer deaths accounting for 90% of all cancer-related deaths. Metastasis is the process of cells disseminating from the primary tumor to a distant tissue of the body. Our goal is to improve our understanding of the metastatic process, and identify vulnerabilities in the metastatic tumor that can be targetable.
The tumor microenvironment of cancer contains various types of cells, such as mesenchymal cells, endothelial cells, fibroblasts, and cells of the immune system including lymphocytes and myeloid cells. The knowledge on the tumor microenvironment in childhood cancers and bone metastases is limited and our lab seeks to explore and expand the knowledge in the role of the tumor microenvironment in cancer development and tumor cell dissemination and cancer resistance.
Brain tumors are the most common solid cancers among children, representing about 20% of all childhood cancers. Childhood brain tumors is the leading cause of cancer-related deaths in children where current treatment options still remain inadequate for relapsed patients. Pursuits to develop new therapy options are highly warranted and therefore one of the main goals of our laboratory.
The main childhood cancers our lab is studying are tumors with embryonic origin. Specifically, neuroblastomas that arise in the sympathetic nervous system, and medulloblastomas that originate in the cerebellum.
When cancer spreads from a primary tumor, it is called metastasis. Metastases account for ~90% of cancer death worldwide. Different cancers tend to spread to different sites, and the most common sites of metastasis are bones. Surgical removal of bone metastatic tumors as curative treatment is not possible and cells in metastatic tumors are very resistant to treatment. The goal of our lab is to provide new insights into the biology of bone metastases from different primary tumor origin with the emphasis of why primary tumors have a propensity to spread to the bone and to delineate cellular and molecular interactions between tumor cells and the tumor microenvironment that cause resistance to treatment.
The development of adult cancers such as prostate cancer and renal cell carcinoma is in many of cases unknown. One of our long-term questions is to provide understanding of the biological mechanism behind why these cancers develop and spread to other organs.
We are using single-cell RNA-sequencing to dissect and catalog tumor tissue at the single cell level. This approach is providing a systematic view on the cellular and molecular key players in the tumor tissue, both during progression of cancer and in the context of treatment resistance.
A major hurdle in preclinical testing of new cancer therapies is modeling cancer in physiological relevant manner that recapitulate the disease in patients.
Our lab is using patient-derived xenograft (PDX) mouse modeling, which is a preclinical mouse model where cancer cells have been isolated from patients and not been grown in plastic or propagated as cell cultures. It is believed that this model conserves the original tumor characteristics such as tumor histology, tumor architecture and tumor growth, that offer relevant predicative insights into clinical outcomes when evaluating the efficacy of novel cancer therapeutics.
Our lab is also using genetically engineered mouse models that spontaneously develop medulloblastomas or neuroblastomas. These mouse models have the same cell of origin and similar genetic features as the human disease, with an intact immune system.
We use primary tissue freshly isolated from patients and animals to study and model cancer.