Cancer biomarkers: Emerging trends and clinical implications for personalized treatment

Cell, Год журнала: 2024, Номер 187(7), С. 1617 - 1635

Опубликована: Март 1, 2024

Язык: Английский

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Circulating tumor nucleic acids: biology, release mechanisms, and clinical relevance

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Янв. 21, 2023

Despite advances in early detection and therapies, cancer is still one of the most common causes death worldwide. Since each tumor unique, there a need to implement personalized care develop robust tools for monitoring treatment response assess drug efficacy prevent disease relapse.

Язык: Английский

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Clinical significance and biology of circulating tumor DNA in high-risk early-stage HER2-negative breast cancer receiving neoadjuvant chemotherapy

Cancer Cell, Год журнала: 2023, Номер 41(6), С. 1091 - 1102.e4

Опубликована: Май 4, 2023

Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized hormone receptor (HR)-positive/HER2-negative triple-negative (TNBC) patients receiving neoadjuvant chemotherapy (NAC) I-SPY2 trial. positivity rates before, during, after NAC are higher TNBC than HR-positive/HER2-negative patients. Early clearance 3 weeks initiation predicts a favorable response to only. Whereas associates with reduced distant recurrence-free survival both subtypes. Conversely, negativity correlates improved outcomes, even extensive residual cancer. Pretreatment mRNA profiling reveals associations between shedding cell cycle immune-associated signaling. On basis these findings, trial will prospectively test for utility redirecting therapy prognosis.

Язык: Английский

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Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options

Cancers, Год журнала: 2023, Номер 15(3), С. 841 - 841

Опубликована: Янв. 30, 2023

The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated success story targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy patients with NSCLC sensitizing EGFR mutations, second-line who present resistance-associated mutation T790M after treatment previous EGFR-TKIs, and adjuvant for early stage resected NSCLC, harboring mutations. Despite durable responses advanced resistance to osimertinib, similar other therapies, inevitably develops. Understanding mechanisms resistance, including both EGFR-dependent -independent molecular pathways, well their therapeutic potential, represents an unmet need thoracic oncology. Interestingly, differential develop when osimertinib administered versus setting, indicating importance selection pressure clonal evolution tumor cells. Standard approaches progression include targetable genetic alteration detected, cytotoxic chemotherapy or without antiangiogenic immunotherapeutic agents. Deciphering how use agents EGFR-positive current challenge clinical research. Emerging options involve combinations different novel EGFR-TKI inhibitors. Research should also be focused on standardization liquid biopsies order facilitate monitoring alterations osimertinib.

Язык: Английский

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Liquid biopsy approaches to capture tumor evolution and clinical outcomes during cancer immunotherapy

Journal for ImmunoTherapy of Cancer, Год журнала: 2023, Номер 11(1), С. e005924 - e005924

Опубликована: Янв. 1, 2023

Circulating cell-free tumor DNA (ctDNA) can serve as a real-time biomarker of burden and provide unique insights into the evolving molecular landscape cancers under selective pressure immunotherapy. Tracking genomic alterations detected in ctDNA may reveal clonal architecture metastatic cascade thus improve our understanding wiring therapeutic responses. While liquid biopsies rapid accurate evaluation dynamics during immunotherapy, complexity antitumor immune responses is not fully captured through single-feature analyses. This underscores need for integrative studies modeling compartment to understand kinetics clearance association with quality Clinical applications testing patients treated checkpoint inhibitors have shown both predictive prognostic value detection biomarkers, such mutational microsatellite instability, well allowing monitoring circulating assessment early on-therapy These efforts highlight emerging role selecting cancer efficacy, determining optimal duration treatment ultimately guiding selection sequencing. The clinical translation propelled by increasing number ctDNA-directed interventional trials immuno-oncology space, signifying critical step towards implementation precision immuno-oncology.

Язык: Английский

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Bridging biological cfDNA features and machine learning approaches

Trends in Genetics, Год журнала: 2023, Номер 39(4), С. 285 - 307

Опубликована: Фев. 13, 2023

Liquid biopsies (LBs), particularly using circulating tumor DNA (ctDNA), are expected to revolutionize precision oncology and blood-based cancer screening. Recent technological improvements, in combination with the ever-growing understanding of cell-free (cfDNA) biology, enabling detection tumor-specific changes extremely high resolution new analysis concepts beyond genetic alterations, including methylomics, fragmentomics, nucleosomics. The interrogation a large number markers complexity data render traditional correlation methods insufficient. In this regard, machine learning (ML) algorithms increasingly being used decipher disease- tissue-specific signals from cfDNA. Here, we review recent insights into biological ctDNA features how these incorporated sophisticated ML applications.

Язык: Английский

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Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 28, 2024

No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility risk stratification unclear. Here, we intersect ctDNA%, treatment outcomes, clinical characteristics across 738 plasma samples from 491 male mCRPC patients two randomized multicentre phase II trials a prospective province-wide blood biobanking program. ctDNA% correlates with serum radiographic metrics of disease burden highest in liver metastases. strongly predicts overall survival, progression-free response independent therapeutic context outperformed established prognostic factors. Recognizing that ctDNA-based biomarker genotyping limited low some patients, leverage the relationship between factors to develop clinically-interpretable machine-learning tool whether patient has sufficient informative ctDNA (available online: https://www.ctDNA.org ). Our results affirm as an actionable provide practical framework optimized testing.

Язык: Английский

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6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7)

The Breast, Год журнала: 2024, Номер 76, С. 103756 - 103756

Опубликована: Май 28, 2024

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at last two ABC conferences (ABC 6 in 2021, virtual, and 7 2023, Lisbon, Portugal), organized by Global Alliance. It provides main recommendations on how to best manage patients with advanced breast cancer (inoperable locally or metastatic), of all subtypes, as well palliative supportive care. These are based available evidence expert opinion when a higher level is lacking. Each guideline accompanied (LoE), grade recommendation (GoR) percentage reached conferences. Updated diagnostic treatment algorithms also provided. The represent management options for living globally, assuming accessibility therapies. Their adaptation (i.e. resource-stratified guidelines) often needed settings where access care limited.

Язык: Английский

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Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort

JAMA Network Open, Год журнала: 2024, Номер 7(1), С. e2351700 - e2351700

Опубликована: Янв. 22, 2024

Importance Tissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline–recommended targeted therapies. Sequencing circulating tumor DNA (ctDNA) also identify tumor-derived mutations, and there increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The value concurrent tissue profiling has not been formally assessed in large, multicancer cohort from heterogeneous settings. Objective To evaluate whether patients concurrently tested both NGS have higher rate detection guideline-based compared alone. Design, Setting, Participants This study comprised 3209 who underwent between May 2020, December 2022, within deidentified, Tempus multimodal database, consisting linked molecular data. Included had stage IV disease (non–small cell lung cancer, breast prostate or colorectal cancer) sufficient blood sample quantities analysis. Exposures Received results plasma genomic profiling, biopsies draws occurring 30 days one another. Main Outcomes Measures Detection rates variants found uniquely by profiling. Results (median age at diagnosis disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) included 1693 women (52.8%). Overall, 1448 (45.1%) variant detected. Of these patients, 9.3% (135 1448) detected 24.2% (351 solid-tissue testing. Although largely concordant another, differences identification actionable either assay varied according to cancer type, gene, variant, burden. 352 20.2% (71 352) unique findings results. Most unique, (55.0% [55 100]) were ESR1 , resulting 24.7% increase (23 93) harboring an mutation relative Conclusions Relevance suggests biomarkers are testing, among cancer. Integration into routine management advanced cancers may expand delivery molecularly guided therapy improve patient outcomes.

Язык: Английский

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Beyond blood: Advancing the frontiers of liquid biopsy in oncology and personalized medicine

Cancer Science, Год журнала: 2024, Номер 115(4), С. 1060 - 1072

Опубликована: Фев. 3, 2024

Abstract Liquid biopsy is emerging as a pivotal tool in precision oncology, offering noninvasive and comprehensive approach to cancer diagnostics management. By harnessing biofluids such blood, urine, saliva, cerebrospinal fluid, pleural effusions, this technique profiles key biomarkers including circulating tumor DNA, cells, microRNAs, extracellular vesicles. This review discusses the extended scope of liquid biopsy, highlighting its indispensable role enhancing patient outcomes through early detection, continuous monitoring, tailored therapy. While advantages are notable, we also address challenges, emphasizing necessity for precision, cost‐effectiveness, standardized methodologies broader application. The future trajectory set expand reach personalized medicine, fueled by technological advancements collaborative research.

Язык: Английский

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