The Role and Impact of Minimal Residual Disease in NSCLC.
Ontology highlight
ABSTRACT: Purpose of review
There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer.Recent findings
Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more "targeted" adjuvant treatment.
SUBMITTER: Frisone D
PROVIDER: S-EPMC8568856 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly diagnose the presence of MRD. Liquid biopsies thus have the potential to detect MRD, allowing, among other things, the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor-specific microRNA. Although liquid biopsy is increasingly studied, several technical issues still limit its clinical applicability: low sensitivity, poor standardization or reproducibility, and lack of randomized trials demonstrating its clinical benefit. Being able to detect MRD could give clinicians a more comprehensive view of the risk of relapse of their patients and could select patients requiring treatment escalation with the goal of improving cancer survival. In this review, we are discussing the different methodologies used and investigated to detect MRD in solid cancers, their respective potentials and issues, and the clinical impacts that MRD detection will have on the management of cancer patients.
| S-EPMC8582541 | biostudies-literature
Project description:BackgroundObesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models.MethodsDoxycycline-inducible primary mammary tumors were generated in intact MMTV-rtTA;TetO-HER2/neu (MTB/TAN) mice or orthotopic recipients fed a high-fat diet (HFD; 60% kcal from fat) or a control low-fat diet (LFD; 10% kcal from fat). Following oncogene downregulation and tumor regression, mice were followed for clinical recurrence. Body weight was measured twice weekly and used to segregate HFD mice into obese (i.e., responders) and lean (i.e., nonresponders) study arms, and obesity was correlated with body fat percentage, glucose tolerance (measured using intraperitoneal glucose tolerance tests), serum biomarkers (measured by enzyme-linked immunosorbent assay), and tissue transcriptomics (assessed by RNA sequencing). MRD was quantified by droplet digital PCR.ResultsHFD-Obese mice weighed significantly more than HFD-Lean and LFD control mice (p < 0.001) and had increased body fat percentage (p < 0.001). Obese mice exhibited fasting hyperglycemia, hyperinsulinemia, and impaired glucose tolerance, as well as decreased serum levels of adiponectin and increased levels of leptin, resistin, and insulin-like growth factor 1. Tumor recurrence was accelerated in HFD-Obese mice compared with HFD-Lean and LFD control mice (median relapse-free survival 53.0 days vs. 87.0 days vs. 80.0 days, log-rank p < 0.001; HFD-Obese compared with HFD-Lean HR 2.52, 95% CI 1.52-4.16; HFD-Obese compared with LFD HR 2.27, 95% CI 1.42-3.63). HFD-Obese mice harbored a significantly greater number of residual tumor cells than HFD-Lean and LFD mice (12,550 ± 991 vs. 7339 ± 2182 vs. 4793 ± 1618 cells, p < 0.001).ConclusionThese studies provide a genetically engineered mouse model for study of the association of diet-induced obesity with breast cancer recurrence. They demonstrate that this model recapitulates physiological changes characteristic of obese patients, establish that the association between obesity and recurrence risk is causal in nature, and suggest that obesity is associated with the increased survival and persistence of residual tumor cells.
| S-EPMC6416940 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-08-06 | GSE242746 | GEO
Project description:Progression from localized to metastatic disease requires cancer cells spreading to distant organs through the bloodstream. Only a small proportion of these circulating tumor cells (CTCs) survives dissemination due to anoikis, shear forces and elimination by the immune system. However, all metastases originate from CTCs capable of surviving and extravasating into distant tissue to re-initiate a tumor. Metastasis initiation is not always immediate as disseminated tumor cells (DTCs) may enter a non-dividing state of cell dormancy. Cancer dormancy is a reversible condition that can be maintained for many years without being clinically detectable. Subsequently, late disease relapses are thought to be due to cancer cells ultimately escaping from dormant state. Cancer dormancy is usually associated with minimal residual disease (MRD), where DTCs persist after intended curative therapy. Thus, MRD is commonly regarded as an indicator of poor prognosis in all cancers. In this review, we examine the current understanding of MRD and immunity during cancer progression to metastasis and discuss clinical perspectives for oncology.
| S-EPMC7909268 | biostudies-literature
Project description:The identification of patients at high risk of relapse is a critical goal of modern translational research in oncohematology. Minimal residual disease (MRD) detection by polymerase chain reaction-based methods is routinely employed in the management of patients with acute lymphoblastic leukemia. Current knowledge indicates that it is also a useful prognostic tool in several mature lymphoproliferative disorders and particularly in follicular lymphoma (FL). Based on this evidence clinical trials employing MRD-based risk stratification are currently ongoing in FL. In this review the 'state of the art' of MRD evaluation in FL is discussed. A short description of technical issues and recent methodological advances is provided. Then, the bulk of the review focuses on critical take-home messages for clinicians working in the field. Finally, we discuss future perspectives of MRD detection and more generally outcome prediction in FL.
| S-EPMC3666448 | biostudies-literature
Project description:Many patients with advanced cancers achieve dramatic responses to a panoply of therapeutics, yet retain minimal residual disease (MRD), which ultimately results in relapse. To gain insights into the biology of MRD we applied single-cell RNA-sequencing to malignant cells isolated from BRAF-mutant patient-derived xenograft (PDX) melanoma cohorts exposed to concurrent RAF/MEK-inhibition.
2018-07-18 | GSE116237 | GEO
Project description:Multiple Myeloma (MM), the second most common hematologic malignancy, has been the target of many therapeutic advances over the past two decades. The introduction of novel agents, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, along with autologous hematopoietic stem cell transplantation (ASCT) in the current standard of care, has increased the median survival of myeloma patients significantly. Nevertheless, a curative treatment option continues to elude us, and MM remains an incurable disease, with patients relapsing even after achieving deep conventionally defined responses, underscoring the need for the development of sensitive methods that will allow for proper identification and management of the patients with a higher probability of relapse. Accurate detection of Minimal Residual Disease (MRD) from a bone marrow biopsy represents a relatively new approach of evaluating response to treatment with data showing clear benefit from obtaining MRD(-) status at any point of the disease course. As life expectancy for patients with MM continues to increase and deep responses are starting to become the norm, establishing and refining the role of MRD in the disease course is more relevant than ever. This review examines the different methods used to detect MRD and discusses future considerations regarding the implementation in day-to-day clinical practice and as a prospective primary endpoint for clinical trials.
| S-EPMC8825476 | biostudies-literature
Project description:Technological advances in the laboratory have led to substantial improvements in clinical decision making through the introduction of pretreatment prognostic risk stratification factors in acute myeloid leukaemia (AML). Unfortunately, similar progress has not been made in treatment response criteria, with the definition of 'complete remission' in AML largely unchanged for over half a century. Several clinical trials have demonstrated that high-sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission, but at increased relapse risk. We review these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and improve clinical use of MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies, such as chronic myelogenous leukaemia and acute promyelocytic leukaemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission and recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as standard of care.
| S-EPMC4163748 | biostudies-literature
Project description:Minimal (or measurable) residual (MRD) disease provides a biomarker of response quality for which there is robust validation in the context of modern intensive treatment for younger patients with Acute Myeloid Leukemia (AML). Nevertheless, it remains a relatively unexplored area in older patients with AML. The lack of progress in this field can be attributed to two main reasons. First, physicians have a general reluctance to submitting older adults to intensive chemotherapy due to their frailty and to the unfavourable biological disease profile predicting a poor outcome following conventional chemotherapy. Second, with the increasing use of low-intensity therapies (i.e., hypomethylating agents) differing from conventional drugs in mechanism of action and dynamics of response, there has been concomitant skepticism that these schedules can produce deep hematological responses. Furthermore, age dependent differences in disease biology also contribute to uncertainty on the prognostic/predictive impact in older adults of certain genetic abnormalities including those validated for MRD monitoring in younger patients. This review examines the evidence for the role of MRD as a prognosticator in older AML, together with the possible pitfalls of MRD evaluation in older age.
| S-EPMC6070940 | biostudies-literature
Project description:Residual tumor cells which remain dormant after MYC inactivation in a primary MYC-HCC derived cell line.
2024-08-06 | GSE242745 | GEO