Liquid biopsies are an emerging technology, a minimally-invasive test that analyzes tumor-derived material from bodily fluids, e.g., blood, saliva, stool, and urine, for the presence of cancer or other abnormal cells. It is relatively new, and research is ongoing to determine its effectiveness and reliability when applied in clinical settings. Potential benefits, including its non-invasive nature, real-time insights on disease progression, and role in informing treatment decisions, make it a promising tool in diagnosing and managing cancer. A recent review of current technology and applications of liquid biopsies found that liquid biopsies are increasingly used for cancer molecular profiling that enables precision oncology – from early diagnosis to management of refractory metastatic disease.
Liquid Biopsies in Oncology
Liquid biopsies have the potential to detect cancers and determine their stages, for real-time monitoring of cancer progression, and for determination of tumor heterogeneity and treatment responses. In addition, liquid biopsies can screen for genetic abnormalities or other pathologic and abnormal conditions. Four major biological agencies present in liquid biopsy samples include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and tumor-educated platelets (TEPs). ctDNA, released by tumor cells after necrosis and apoptosis, is derived from various tumor sites and, therefore, can address tumor heterogeneity, a significant weakness of traditional tissue biopsies. Several techniques, e.g., polymerase chain reaction (PCR), next-generation sequencing (NGS), and digital PCR, can be used for liquid biopsy analysis.
Liquid biopsy is relatively new, and research is ongoing to determine its effectiveness and reliability when applied in clinical settings. Potential benefits, including its non-invasive nature, real-time insights on disease progression, and role in informing treatment decisions, make it a promising tool in diagnosing and managing cancer. A recent review of current technology and applications of liquid biopsies found that liquid biopsies are increasingly used for cancer molecular profiling that enables precision oncology – from early diagnosis to management of refractory metastatic disease.
Liquid biopsy tests approved by the US Food & Drug Administration (FDA) include tests to predict the outcome for patients with metastatic breast, prostate, or colon cancer; to detect a gene mutation common in non-small cell lung cancer (NSCLC), to detect ctDNA and common genetic errors, and to detect mutations in various cancers. Validated and adequately sensitive ctDNA assays can potentially direct targeted therapy for patients with advanced cancer. Just under a year ago, in July 2022, the European Society for Medical Oncology (ESMO) released recommendations on the use of ctDNA assays for patients with cancer.
Liquid Biopsy Potential & Obstacles
Potential
Nanoparticles
Advanced materials like nanoparticles can potentially revamp liquid biopsy technologies while providing reliable and accurate results. Polymers, e.g., smart polymeric materials, can enhance the sensitivity and specificity of liquid biopsies to create personalized treatment plans.
Polymer-based liquid biopsy
Polymer-based liquid biopsy methods detect cancer early and can be helpful for cancer progression and therapy response monitoring. In addition, these methods can provide valuable data on cancer genetics and molecular characteristics, which helps formulate targeted therapies or personalized treatment.
Genetic changes
Findings from the analysis of genetic changes and epigenetic alterations can be applied elsewhere, e.g., cancer screening, prognosis assessment, tumor burden evaluation, and recurrence surveillance.
Mixed clinical responses
Analysis of liquid biopsy samples may also help explain mixed clinical responses to therapy.
Obstacles
Amount of cancer-originated material
An obstacle in creating effective liquid biopsies is the small amount of cancer-originated materials found in a sample, leading to inaccuracies in detecting and analyzing biomarkers. Different technologies and advanced materials can address this.
Non-genetic mechanisms
Using ctDNA in oncology is limited by its inability to detect non-genetic mechanisms of resistance.
Polymeric Surfaces as Platforms
Developments in polymer chemistry have produced interesting structures, e.g., molecularly imprinted polymers, branched polymers, nanopolymer composites, and hybrids. These structures enable enhanced platforms, which positively impact the performance of liquid biopsy analyses.
Standardized Methods
Zaninović et al. (2023) identify the lack of standardized methods for processing and analysis as an obstacle to implementation in clinical practice.
Integrating Liquid Biopsies into Cancer Care
1. Colorectal Cancer (CRC)
CRC diagnosis, prognosis, and therapeutic monitoring depend on tissue biopsy, which has limitations, namely its invasiveness, high cost, and limited applicability in longitudinal monitoring. In contrast, liquid biopsy enables easy sampling, effective monitoring, and longitudinal assessment of treatment dynamics. Liquid biopsy biomarkers currently undergoing research for the diagnosis, prognosis, treatment monitoring, and applicability for personalized management of CRC include novel components of the microbiome, non-coding RNAs, extracellular vesicles, and ctDNA. A study by Chen et al. (2022) on the clinical significance of CTCs in patients with CRC found that total CTCs and mesenchymal CTCs was a valuable biomarker for predicting prognosis.
2. Esophageal Cancer
According to Min et al. (2022), monitoring the dynamic changes of ctDNA helps evaluate the therapeutic efficacy and predict early recurrence in esophageal cancer. The authors stress the importance of establishing standards for individualized ctDNA detection in assessing treatment response and surveillance of esophageal cancer and developing clinical practice guidelines.
3. Gastric Cancer
A review by Zhang et al. (2022) revealed that numerous studies have demonstrated the potential of liquid biopsy in gastric cancer (GC). A ctDNA assay containing the most frequent genomic aberrations and methylation sites can detect early-stage GC.
4. Lung Cancer
CTCs are important biological indicators of lung cancer prognosis, while CTC counting and typing may help diagnose and treat. A study by Xu et al. (2023) demonstrated a high rate of positive CTC detection in patients with lung cancer. The authors also identified important biological indicators for predicting radiotherapy efficacy and prognosis in patients with lung cancer.
Souza et al. (2023) describe liquid biopsies as a promising option for the detection of metastases and local and regional recurrence in lung cancer and present studies demonstrating that liquid biopsies detect metastases with high accuracy and sensitivity, even before detection on imaging scans. In turn, these tests enable early intervention and personalized treatment. The authors conclude that liquid biopsies, while being developed and validated, have great potential for lung cancer metastases and relapse.
5. Multiple Myeloma (MM)
Invasive single-point bone marrow sampling for MM is a painful procedure incapable of capturing tumor heterogeneity. For MM, Li et al. (2023) describe liquid biopsies as allowing the monitoring of treatment response and disease progression and the comprehensive detection of disease burden and molecular alterations. Further, liquid biopsies provide complementary information to conventional detection approaches and improve their prognostic values. A review by Allegra et al. (2022) reports the usefulness of liquid biopsies in evaluating the changing mutational profile of MM as early markers of disease, reliable predictors of prognosis, and less-invasive monitoring tools.
6. Nasopharyngeal carcinoma (NPC)
Gao et al. (2023) found that the number of CTC and MCTCs detected in the peripheral blood of patients with NPC is a useful biomarker for predicting patient progress. Changes in the number of CTC and MCTC were significantly associated with patient therapy.
7. Pediatric Solid Tumors
Liquid biopsy is a promising novel approach in pediatric oncology. Zaninović et al. (2023) caution that further investigation into the physiology of ctDNA release, circulation, and clearance is needed before implementation into clinical practice. In light of the relatively small prevalence of relevant conditions, the authors recommend standardization of procedures of sample collection and harmonization of protocols between extensive collaborative studies to enable the pooling of patient cohorts and merging of data for meta-analyses.
8. Renal cell carcinoma (RCC)
According to Li et al. (2023), the diagnosis and treatment of RCC are challenging due to multiple factors, including unremarkable symptoms of early-stage RCC, the risk of post-op metastasis or recurrence, and low sensitivity to both radiotherapy and chemotherapy. Liquid biopsies have the potential to identify high-risk patients, develop personalized treatment plans, and support precision medicine in RCC. Li et al. (2023) reviewed liquid biopsy components and their clinical applications comprehensively. They found that liquid biopsy is a low-cost, high-efficiency, and high-accuracy clinical detection method for RCC. A study on metastatic RCC by Koh et al. (2022) discovered that early ctDNA dynamics can predict response to immune checkpoint inhibitors.
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