Patient-derived xenograft models of colorectal cancer in combination therapy

Field: Cancers

Location:  Ochsner Clinical School

Type of student:  Both types will be considered (i.e. you are flexible with your project/s)

Type of work: Chart reviews, Literature review, Statistical analysis, Web lab work

Brief Synopsis: CRC is the third most common cancer and the second leading cause of cancer-related mortality, with an estimated incidence of 143,000 cases and 51,000 deaths per year in the United States. Despite optimal oncologic treatment, including surgery, chemotherapy, and/or radiotherapy, up to 50% of stage II and III CRC patients will develop extra- nodal metastases. This is the most significant negative determinant of CRC morbidity and mortality. Based on work from our group and others, we identified a unique class of cells, CRC tumor-initiating cells (Co-TIC), which are responsible for CRC growth, drug resistance, and subsequent extra-nodal metastasis. These cells were shown to express the cell surface markers CD133 and CXCR4. We have further found that Co-TIC involvement in these processes is largely dependent on lymph node stromal cell. We hypothesize that the LN microenvironment is responsible for supporting CD133+CXCR4+ Co-TIC in CRC growth and extra-nodal metastasis via providing CXCL12 that primes and stimulates Co-TIC. There is increasing evidence that the lymph node microenvironment play a significant role in cellular communication resulting in CRC tumor growth, drug resistance, and subsequent extra-nodal metastasis. This project is to use patient-derived xenograft models of colorectal cancer for combination therapy targeting Co-TIC in addition to conventional chemotherapy.

Time frame: Open time frame