Liquid Biopsies

The future of liquid biopsies Despite the advances being made, several hurdles need to be overcome before liquid biopsies can reach their full potential and promise. Liquid Biopsies What are liquid biopsies? What benefits do liquid biopsies offer? In this infographic, we take a look at the benefits liquid biopsies can offer and explore some examples of recent developments in this field. A liquid biopsy involves the sampling and analysis of body fluids, such as blood, urine, saliva or cerebral spinal fluid, to look for signs associated with cancer or other diseases. Liquid biopsies enable clinicians to collect and analyze samples which might not be possible with “gold standard” tissue biopsies, due to the location of the tissue of interest. These features mean that liquid biopsies can be an incredibly useful tool to provide comprehensive information about the complexity of an individual’s disease and how it is changing over time or responding to treatment. Liquid biopsies can also detect markers of both interpatient and intratumor heterogeneity. This can enable clinicians to tailor a patient’s treatment, as specific mutations can be associated with expected responses to a particular treatment. Liquid biopsies can be used to analyze a range of biomarker types, including: Whole cells, such as circulating tumor cells (CTCs) Extracellular vesicles (EVs), such as exosomes Cell-free DNA (cfDNA) and RNA (cfRNA), including circulating tumor DNA (ctDNA), mitochondrial DNA (mtDNA) and cell-free fetal DNA (cffDNA) Tumor CTCs EVs cfDNA Compared to standard tissue biopsies, liquid biopsies are typically: Rapid Able to provide real-time information Lower risk More likely to identify rare cell subpopulations Minimally invasive Amenable to repeated sampling In oncology, liquid biopsies can be used for: Primary tumor diagnosis Therapy monitoring Minimal residual disease detection Determination of suitability of a treatment Tumor heterogeneity evaluation Recent developments in liquid biopsies There is a great interest in developing liquid biopsies to harness the benefits they can offer, particularly for improving the detection and monitoring of cancers. Recent progress in this area includes: A novel liquid biopsy approach, ACT-Discover (Aneuploidy in ctDNA), was shown to be 30% more sensitive than current methods at detecting ctDNA in pancreatic cancer patients. Researchers identified a serum biomarker specific to intrahepatic cholangiocarcinoma, an aggressive type of liver cancer. Changes in N-glycan were detected in blood samples just as well as in tissue samples and could help to speed up diagnosis. The detection of CX3CR1, a biomarker expressed on T cells, could help to predict non-small cell lung cancer patients’ responses to a combination of immune checkpoint inhibitor therapy and chemotherapy. Elevated levels of the biomarker were associated with tumor shrinkage and cancer remission. Mutations associated with recurrent breast cancer were detected in cfDNA by liquid biopsy a few months before recurrent cancer was detected at a regular follow-up appointment. Researchers were also able to assess changes in intratumoral heterogeneity. Neoadjuvant therapy (NAT) can be added to surgery as part of treatment approaches to esophageal squamous cell carcinoma (ESCC) but can lead to worse outcomes in some patients. A liquid biopsy based on a panel of mRNA and microRNA biomarkers was developed to predict ESCC patients’ response to NAT. More sensitive pancreatic cancer detection Earlier detection of lethal liver cancer Predicting chemoimmunotherapy response Improved monitoring of breast cancer progression Predicting resistance to NAT Transplant monitoring In addition to cancer applications, liquid biopsies are also being pursued for other areas, including transplant monitoring and prenatal testing. Liquid biopsies are being investigated for their use as a tool to monitor post-transplant rejection, infection and immunosuppression. Currently, heart transplant patients are monitored for signs of organ rejection by endomyocardial biopsy. A pilot study found that liquid biopsy results of donor-derived cfDNA showed high homogeneity with endomyocardial biopsy results, highlighting the potential for a new, less-invasive method of diagnosis. Donor-derived cfDNA was also used to diagnose allograft rejection in thoracic organ transplant recipients. The cost-effective method was able to diagnose rejection in 66.6% of patients whilst circumventing the risk of scarring associated with repeated surgical biopsies. Heart transplant monitoring Allograft rejection detection Non-invasive prenatal testing and maternal health During pregnancy, molecular messages pass between the mother and baby through the placenta. These biomarkers can be detected in maternal blood and used to screen for fetal abnormalities. Non-invasive prenatal testing (NIPT) offers risk-free screening for patients, avoiding complications such as miscarriage which can be associated with traditional invasive testing methods like amniocentesis. Liquid biopsies are also increasingly being explored as tools for monitoring maternal health and pregnancy-related complications. Blood samples from pregnant mothers were used to discover cfRNA transcriptomic changes associated with preeclampsia. This led to the identification of a panel of 18 genes that could form the basis of a liquid biopsy test to predict preeclampsia. Early prediction of preeclampsia EV phenotypes and concentrations were analyzed in women with uncomplicated pregnancies to create a specific EV signature. Liquid biopsies could be developed to identify changes in this signature that are associated with pathological conditions such as preeclampsia or preterm birth. Extracellular vesicles as markers of pregnancy complications Several studies have documented cases of maternal malignancy being identified by NIPT, highlighting the potential for NIPT sequencing abnormalities to alert clinicians to complete further investigations. Detecting maternal cancer Improvements are needed in: Specificity Detecting highly specific biomarkers is necessary to prevent misdiagnosis. Liquid biopsies must accurately distinguish disease biomarkers from healthy markers. Sensitivity Many of the biomarkers that liquid biopsies look for are present at incredibly low concentrations, especially at presymptomatic stages of cancer. Technologies are needed that can improve the detection of these “needles in haystacks”. Standardization Efforts are needed to standardize and improve pre-analytical tools and procedures to reduce the chances of errors and associated suboptimal treatment decisions. Computational analysis New tools are needed that are capable of improving data interpretation. Sponsored by: