About this Research Topic
Although early detection of solid tumors allows for curative systemic and local treatments, the risk of developing metastatic disease persists for years after diagnosis. Radiographic monitoring is effective in detecting clinical relapse, while the advancement of circulating tumor DNA (ctDNA) assays has enhanced the capability to detect molecular relapses in the absence of overt metastases, establishing the concept of minimal residual disease (RD). Nowadays, liquid biopsy is increasingly used for Minimal RD detection to accurately manage disease monitoring, becoming a more routine approach used to predict prognosis and monitor relapse in cancer patients. However, it is still unclear whether changing treatment strategies in response to ctDNA detection (namely molecular RD, MRD) will improve survival outcomes. Moreover, other tumor-derived analytes in peripheral blood are being tested for early cancer detection, with the introduction of other concepts such as cellular residual disease (CRD) in cases where circulating tumor cells (CTCs) are detected.
Different studies have established the predictive value of molecular residual disease (MRD) for relapse in various solid tumors, especially colon rectal cancer (CRC), non-small cell lung cancer (NSCLC), and breast cancer (BC). However, many questions remain unresolved regarding the interpretation and practical application of these tests in clinical settings. Tumor-informed assays can trace the original genomic signature of the primary tumor. Despite that, their limited capacity to capture the mutational landscape, coupled with the requirement for sufficient tumor tissue, makes them less suitable for monitoring metastatic clonal evolution and increases the risk of false negative results. On the other hand, tumor-naïve technologies can simplify MRD application by combining multimodal profiling, such as genomic and epigenomic characterization. The low number of circulating tumor cells (CTCs) shed by the tumor into the bloodstream justifies the infrequent use of CTCs in early settings, necessitating a multifaceted approach. Moreover, the optimal time points for blood collection still need clarification due to the wide range of median lead times from MRD detection to macroscopic relapse.
Nowadays, authoritative organizations such as the National Cancer Institute (NCI) and the Food and Drug Administration (FDA) strongly recommend MRD testing. Prognostic stratification, recurrence monitoring, and treatment guidance are established as the main fields of application for these new technologies. Moreover, ongoing clinical trials are testing the escalation therapeutic strategy in the context of MRD detection, with the potential use of targeted drugs. Much remains to be discovered about how clinicians should act when faced with a positive MRD test in the early setting, and data are still lacking on a de-escalation treatment strategy when disease monitoring with MRD consistently shows negative results. The purpose of this research topic collection is to provide readers with a comprehensive overview of the use of MRD and CRD in the early setting, with a focus also on new evidence regarding molecular cancer-screening, the initial results of which are beginning to emerge.
We welcome Original Research, Review, Mini Review, Metanalysis, and Perspective articles on themes including, but not limited to:
• Molecular Residual Disease (MRD)
• Early detection
• Cellular Residual Disease (CRD)
• Molecular cancer- screening
Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not in scope for this collection.
Please note the following conflict of interest disclosures for Dr. Gerratana:
- Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, Abbvie
- Research Funding: Menarini Silicon Biosystems
- Travel Expenses: Menarini Stemline, Novartis
Dr. Pontolillo declared the following conflict of interest:
- Travel grants: Pfizer, Eli Lilly
Dr. Reduzzi declared no conflict of interest.
Different studies have established the predictive value of molecular residual disease (MRD) for relapse in various solid tumors, especially colon rectal cancer (CRC), non-small cell lung cancer (NSCLC), and breast cancer (BC). However, many questions remain unresolved regarding the interpretation and practical application of these tests in clinical settings. Tumor-informed assays can trace the original genomic signature of the primary tumor. Despite that, their limited capacity to capture the mutational landscape, coupled with the requirement for sufficient tumor tissue, makes them less suitable for monitoring metastatic clonal evolution and increases the risk of false negative results. On the other hand, tumor-naïve technologies can simplify MRD application by combining multimodal profiling, such as genomic and epigenomic characterization. The low number of circulating tumor cells (CTCs) shed by the tumor into the bloodstream justifies the infrequent use of CTCs in early settings, necessitating a multifaceted approach. Moreover, the optimal time points for blood collection still need clarification due to the wide range of median lead times from MRD detection to macroscopic relapse.
Nowadays, authoritative organizations such as the National Cancer Institute (NCI) and the Food and Drug Administration (FDA) strongly recommend MRD testing. Prognostic stratification, recurrence monitoring, and treatment guidance are established as the main fields of application for these new technologies. Moreover, ongoing clinical trials are testing the escalation therapeutic strategy in the context of MRD detection, with the potential use of targeted drugs. Much remains to be discovered about how clinicians should act when faced with a positive MRD test in the early setting, and data are still lacking on a de-escalation treatment strategy when disease monitoring with MRD consistently shows negative results. The purpose of this research topic collection is to provide readers with a comprehensive overview of the use of MRD and CRD in the early setting, with a focus also on new evidence regarding molecular cancer-screening, the initial results of which are beginning to emerge.
We welcome Original Research, Review, Mini Review, Metanalysis, and Perspective articles on themes including, but not limited to:
• Molecular Residual Disease (MRD)
• Early detection
• Cellular Residual Disease (CRD)
• Molecular cancer- screening
Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not in scope for this collection.
Please note the following conflict of interest disclosures for Dr. Gerratana:
- Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, Abbvie
- Research Funding: Menarini Silicon Biosystems
- Travel Expenses: Menarini Stemline, Novartis
Dr. Pontolillo declared the following conflict of interest:
- Travel grants: Pfizer, Eli Lilly
Dr. Reduzzi declared no conflict of interest.
Keywords: Liquid biopsy, early detection, cancer interception, cell free DNA, circulating tumor cells
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