Improvements in animal models for cancer have revolutionized how anti-cancer drugs are evaluated and developed. Patient-derived xenograft (PDX) models have been particularly powerful tools since they use patient-derived tumor tissue engrafted into mice. Tumor cell lines, solid tumor tissue, or hematological tumors can be transplanted into immunodeficient mice. These immunocompromised mice can also be made to have “humanized” immune systems or express components of the human immune system, like immune checkpoint inhibitors, to better screen for the effectiveness of various anti-cancer treatments.
In this era of rapid, high-throughput DNA sequencing, individual tumors can be sequenced and specific defects in DNA damage repair pathways can be defined. This same tumor tissue can be engrafted into a PDX mouse model for screening of drugs or therapeutics that tackle the appropriate DNA damage repair defect. This approach is powerful for screening preclinical drug candidates for efficacy against a range of tumors and it also provides insights into potential off-target effects or toxicities. From the patient perspective, pre-screening potential treatment options in mice can lead to the selection of the most appropriate drug or therapeutic and helps avoid treatments that may be ineffective.
DNA damage events can lead to tumor growth and this area of research continues to inform drug development on the bench and patient care in the clinic.