Improving sensitivity and success of liquid cancer biopsy in mice

Intravenous nanoparticle priming agents given hours before a blood draw greatly increase the sensitivity to liquid biopsies for detecting cancer, according to a preclinical study in mice. In these animals, the approach increased the sensitivity for detection of small tumors from 10% to 75%. “Just as iodinated and gadolinium contrast agents greatly improve the sensitivity of clinical imaging, we envision that molecular priming agents can boost the sensitivity of liquid biopsies in cancer care and for indications beyond oncology,” write the authors. Liquid biopsies such as blood draws are a source of biological substances such as cell-free DNA (cfDNA), enabling diagnosis, monitoring, and genetic profiling of diseases. For example, blood taken from cancer patients contains tumor-derived genetic fragments or circulating tumor DNA (ctDNA). Thus, liquid biopsy offers a noninvasive approach to tumor analysis instead of surgical tumor biopsies. However, the sensitivity of liquid biopsies remains inadequate for many oncological applications – ctDNA is usually scarce in collected blood samples, and it can be difficult or dangerous to draw the large volumes of blood required for effective sequencing or detection, particularly when tumors are small or their locations unknown. To address this challenge, Carmen Martin-Alonso, Shervin Tabrizi, Kan Xiong, and colleagues developed two intravenous priming agents that delay the destruction of cfDNA in vivo so that more remains in the bloodstream when a liquid biopsy is taken, thus increasing the sensitivity of detection, even in smaller blood volumes. According to the authors, the priming agents consisted of liposomal nanoparticles that act on the cells that mediate cfDNA clearance and DNA-binding antibodies that protect cfDNA from enzymatic digestion. Martin-Alonso, Tabrizi, Xiong et al. demonstrate proof-of-concept of the approach using mouse models of cancer and show that, when administered 1 to 2 hours before a blood draw, both priming agents improved the recovery of cfDNA and ctDNA molecules by more than 10-fold and increased the sensitivity for detection of small tumors from less than 10% to more than 75%. “Although this approach enabled improved recovery of tumor genomes and may substantially enhance the sensitivity of ctDNA diagnostic assays, it remains to be determined how such strategies would translate into humans in terms of formulation testing and tolerability,” write Tina Moser and Ellen Heitzer in a related Perspective.