scholarly journals Towards Circulating-Tumor DNA-Based Precision Medicine

2019 ◽  
Vol 8 (9) ◽  
pp. 1365 ◽  
Author(s):  
Ai Hironaka-Mitsuhashi ◽  
Anna Sanchez Calle ◽  
Takahiro Ochiya ◽  
Shin Takayama ◽  
Akihiko Suto
Keyword(s):  
Decision Making ◽  
Precision Medicine ◽  
Clonal Evolution ◽  
Predictive Biomarkers ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Cancer Management ◽  
Cancer Breast ◽  
Metastatic Setting

In the era of precision medicine, targeted therapies have been implemented for various diseases. Genomic information guides decision-making in cancer treatment. The improvements in next-generation sequencing and polymerase chain reaction have made it possible to access the genetic information using circulating-tumor DNAs (ctDNAs). Molecular characteristics of individual tumors can be obtained by analysis of ctDNAs, thus making them excellent tools to guide decision-making during treatment. In oncology, the use of ctDNAs in clinical practice is now gaining importance. Molecular analysis of ctDNAs has potential for multiple clinical applications, including early diagnosis, prognosis of disease, prognostic and/or predictive biomarkers, and monitoring response to therapy and clonal evolution. In this paper, we highlight the applications of ctDNAs in cancer management, especially in metastatic setting, and summarize recent studies about the use of ctDNAs as predictive biomarkers for the therapeutic adaptation/response in lung cancer, breast cancer, and colorectal cancer. These studies offer the evidence to use ctDNAs as a promising approach to solve unmet clinical needs.

scholarly journals Patient-Derived Xenograft and Organoid Models for Precision Medicine Targeting of the Tumour Microenvironment in Head and Neck Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3743
Author(s):  
Tet Woo Lee ◽  
Amy Lai ◽  
Julia K. Harms ◽  
Dean C. Singleton ◽  
Benjamin D. Dickson ◽  
...  
Keyword(s):  
Head And Neck ◽  
Precision Medicine ◽  
Patient Survival ◽  
Predictive Biomarkers ◽  
Tumour Microenvironment ◽  
Response To Therapy ◽  
Preclinical Models ◽  
Therapeutic Success ◽  
Patient Derived Xenograft ◽  
Individualise Therapy

Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the use of predictive biomarkers and stratification strategies offer opportunities to improve therapeutic success in HNSCC. To enable precision medicine of HNSCC, an understanding of the microenvironment that influences tumour growth and response to therapy is required alongside research tools that recapitulate the features of human tumours. In this review, we highlight the importance of the tumour microenvironment in HNSCC, with a focus on tumour hypoxia, and discuss the fidelity of patient-derived xenograft and organoids for modelling human HNSCC and response to therapy. We describe the benefits of patient-derived models over alternative preclinical models and their limitations in clinical relevance and how these impact their utility in precision medicine in HNSCC for the discovery of new therapeutic agents, as well as predictive biomarkers to identify patients’ most likely to respond to therapy.

scholarly journals Molecular Characterization of Prostate Cancers in the Precision Medicine Era

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4771
Author(s):  
Emilio Francesco Giunta ◽  
Laura Annaratone ◽  
Enrico Bollito ◽  
Francesco Porpiglia ◽  
Matteo Cereda ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Circulating Tumor Dna ◽  
Molecular Tests ◽  
Repair Deficiency ◽  
Metastatic Setting ◽  
Pros And Cons ◽  
Prostate Cancers ◽  
Optimal Therapeutic Strategy ◽  
Pathway Deregulation

Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients’ outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.

Will the “new biology” Affect the Future of Histopathology?

2001 ◽  
Vol 16 (1) ◽  
pp. 1-4 ◽  
Author(s):  
A. Carbone
Keyword(s):  
Molecular Techniques ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Cancer Management ◽  
Molecular Tests ◽  
Specific Tumor ◽  
Diagnosis And Classification ◽  
New Biology ◽  
The Impact

The technologies used in histopathology are changing as a consequence of the current revolutionary progress in several areas of biology. It is likely that general cancer management will improve because of the impact of molecular techniques and immunohistochemistry on tumor diagnosis and classification and on the determination of prognosis and response to therapy. Moreover, as therapies are starting to be modelled after the distinctive molecular characteristics of a specific tumor, the availability of molecular tests to all patients will become a matter of great importance.

Personalizing Colon Cancer Adjuvant Therapy: Selecting Optimal Treatments for Individual Patients

2015 ◽  
Vol 33 (16) ◽  
pp. 1787-1796 ◽  
Author(s):  
Rodrigo Dienstmann ◽  
Ramon Salazar ◽  
Josep Tabernero
Keyword(s):  
Colon Cancer ◽  
Early Stage ◽  
Tumor Staging ◽  
Predictive Biomarkers ◽  
Postoperative Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Molecular Characteristics ◽  
Early Stage Disease ◽  
Metastatic Setting

For more than three decades, postoperative chemotherapy—initially fluoropyrimidines and more recently combinations with oxaliplatin—has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice.

scholarly journals Clonal origin and spread of metastatic prostate cancer

2016 ◽  
Vol 23 (4) ◽  
pp. R207-R217 ◽  
Author(s):  
Jamie L Van Etten ◽  
Scott M Dehm
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Large Scale ◽  
Clonal Evolution ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Small Scale ◽  
Genetic Evolution ◽  
Castration Resistant Prostate Cancer ◽  
Origin And Evolution

Metastatic disease is responsible for the majority of prostate cancer deaths. The standard treatment for metastatic disease is surgical or chemical castration in the form of androgen deprivation therapy. Despite initial success and disease regression, resistance to therapy ultimately develops and the disease transitions to castration-resistant prostate cancer, which is uniformly fatal. Thus, developing an understanding of genetic evolution in metastasis and in response to therapy has been a focus of recent studies. Large-scale sequencing studies have provided an expansive catalog of the mutation events that occur in the prostate cancer genome at various stages of disease progression. Small-scale studies have interrogated the genomic composition of multiple metastatic sites within individual patients or have tracked clonal evolution longitudinally in tissues, circulating tumor cells, or circulating tumor DNA. Collectively, these efforts have provided a new conceptual framework for understanding the origin of prostate cancer, as well as the origin and evolution of metastatic disease. In this review, we highlight these recent insights into the spatiotemporal landscape of genetic evolution of prostate cancer.

Cell-free circulating tumor DNA (cfDNA) analysis of advanced thymic epithelial tumors (TETs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8577-8577
Author(s):  
Hiba I. Dada ◽  
Leylah Drusbosky ◽  
Giuseppe Giaccone
Keyword(s):  
Statistical Significance ◽  
Circulating Tumor Dna ◽  
Small Sample ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Genomic Alterations ◽  
Thymic Epithelial Tumors ◽  
Epithelial Tumors ◽  
Tumor Dna ◽  
Thymic Carcinomas

8577 Background: Thymic epithelial tumors (TETs) are rare tumors originating from the epithelial cells of the thymus. Thymomas tend to be slowly growing, whereas thymic carcinomas are more aggressive and often metastasize wildly. TETs have a very low tumor mutational burden (TMB). cfDNA has been used in several tumor types to describe the molecular characteristics and select treatment options, especially in absence of tissue availability. There is no information on the cfDNA detected in TETs. The purpose of this study was to identify common genomic alterations occurring in circulating tumor DNA (ctDNA) in patients with advanced TETs, detected using a cfDNA assay. Methods: We retrospectively evaluated 157 TET samples from the Guardant Health database between November 2017 – November 2020. The cfDNA analysis interrogated single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 83 genes using a commercially available liquid biopsy assay (Guardant360; Guardant Health, Redwood City, CA) . We evaluated the frequency of genomic alterations based on diagnosis, age, and sex. Results: In this cohort, 66% of the patients had thymic carcinoma and 34% had thymoma. The median age was 60 years, and 59% of patients were male. 126 patients (80%) of this cohort had ≥1 somatic alteration detected. The most prevalent mutations detected are TP53 (55%), KIT (13%), EGFR (12%), BRCA2 (11%), PIK3CA (10%), ARID1A (10%), ATM (10%), KRAS (9%), APC (9%), and BRAF (9%). Mutations were more commonly observed in thymic carcinomas than thymomas, but statistical significance was not reached due to the small sample size. Frequencies of the observed genomic alterations are shown in the table below. Conclusions: This study confirms that advanced stage TETs shed tumor DNA into the circulation that can be picked up in the majority of patients, using a solid tumor platform, despite the low TMB typically observed in these tumors. This assay can potentially be used to monitor response to therapy. A more targeted gene panel, enriched for genes commonly mutated in TETs (e.g. GTF2I, BAP1, CYLD) might provide further insights in the future in the management of TETs.[Table: see text]

scholarly journals Precision medicine applications in prostate cancer

2018 ◽  
Vol 10 ◽  
pp. 175883591877692 ◽  
Author(s):  
Edel M. McCrea ◽  
Daniel K. Lee ◽  
Tristan M. Sissung ◽  
William D. Figg
Keyword(s):  
Prostate Cancer ◽  
Precision Medicine ◽  
Resistance Mechanisms ◽  
Response To Therapy ◽  
Cancer Management ◽  
Integral Component ◽  
Prostate Cancer Management

Aided by developments in diagnostics and therapeutics, healthcare is increasingly moving toward precision medicine, in which treatment is customized to each individual. We discuss the relevance of precision medicine in prostate cancer, including gene targets, therapeutics and resistance mechanisms. We foresee precision medicine becoming an integral component of prostate cancer management to increase response to therapy and prolong survival.

scholarly journals Liquid Biopsies for Molecular Biology-Based Radiotherapy

2021 ◽  
Vol 22 (20) ◽  
pp. 11267
Author(s):  
Erik S. Blomain ◽  
Everett J. Moding
Keyword(s):  
Clonal Evolution ◽  
Tumor Biology ◽  
Acquired Resistance ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Treatment Modalities ◽  
Liquid Biopsies ◽  
Invasive Approach ◽  
Molecular Alterations ◽  
Molecular Abnormalities

Molecular alterations drive cancer initiation and evolution during development and in response to therapy. Radiotherapy is one of the most commonly employed cancer treatment modalities, but radiobiologic approaches for personalizing therapy based on tumor biology and individual risks remain to be defined. In recent years, analysis of circulating nucleic acids has emerged as a non-invasive approach to leverage tumor molecular abnormalities as biomarkers of prognosis and treatment response. Here, we evaluate the roles of circulating tumor DNA and related analyses as powerful tools for precision radiotherapy. We highlight emerging work advancing liquid biopsies beyond biomarker studies into translational research investigating tumor clonal evolution and acquired resistance.

scholarly journals Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4743
Author(s):  
Emilie Moati ◽  
Valerie Taly ◽  
Simon Garinet ◽  
Audrey Didelot ◽  
Julien Taieb ◽  
...  
Keyword(s):  
Residual Disease ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Cancer Management ◽  
Metastatic Setting ◽  
Gi Cancers ◽  
Tumor Dna

Gastrointestinal (GI) cancers are major health burdens worldwide and biomarkers are needed to improve the management of these diseases along their evolution. Circulating tumor DNA (ctDNA) is a promising non-invasive blood and other bodily-fluid-based biomarker in cancer management that can help clinicians in various cases for the detection, diagnosis, prognosis, monitoring and personalization of treatment in digestive oncology. In addition to the well-studied prognostic role of ctDNA, the main real-world applications appear to be the assessment of minimal residual disease to further guide adjuvant therapy and predict relapse, but also the monitoring of clonal evolution to tailor treatments in metastatic setting. Other challenges such as predicting response to treatment including immune checkpoint inhibitors could also be among the potential applications of ctDNA. Although the level of advancement of ctDNA development in the different tumor localizations is still inhomogeneous, it might be now reliable enough to be soon used in clinical routine for colorectal cancers and shows promising results in other GI cancers.

Integrating Biomarkers and Targeted Therapy Into Colorectal Cancer Management

2019 ◽  
pp. 207-215 ◽  
Author(s):  
Christopher H. Lieu ◽  
Ryan B. Corcoran ◽  
Michael J. Overman
Keyword(s):  
Colorectal Cancer ◽  
Decision Making ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Prognostic Indicators ◽  
Molecular Characteristics ◽  
Cancer Management ◽  
The Past

There have been substantial advances in the treatment of metastatic colorectal cancer (mCRC) over the past 15 years. Molecular characteristics of mCRC and identification of specific mutations can serve as predictive and prognostic indicators of disease and response to targeted therapies. When incorporated into clinical decision-making, these biomarkers can serve as critical tools in personalizing therapy to ensure the best outcomes. Additional improvements in the survival of patients with mCRC will be made possible with the identification of new predictive molecular biomarkers and their evaluation using rational and innovative clinical trials.

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