Precision Medicine Tools to Guide Therapy and Monitor Response to Treatment in a HER-2+ Gastric Cancer Patient: Case Report

Aguilar‐Mahecha, Adriana; Joseph, Sarah; Cavallone, Luca; Buchanan, Marguerite; Krzemien, Urszula; Batist, Gerald; Basik, Mark

doi:10.3389/fonc.2019.00698

Cited by 8 publications

(5 citation statements)

References 33 publications

(31 reference statements)

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“…Improving technologies have enabled a more comprehensive molecular analysis in the body fluids of patients with cancer and have revealed that circulating tumor-derived molecules could provide multilayer molecular information suitable for cancer diagnostics, prognosis, or even response to therapy (6)(7)(8). The currently available studies analyzing ctDNA alterations in GC focus on a limited number of well-known oncogenes such as TP53 (6) and HER2 (9)(10)(11). On the other hand, studies implementing high-throughput technologies such as new generation sequencing (NGS) are still very scarce and have been mostly conducted in Asian populations (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Liquid Biopsy in Gastric Cancer: Analysis of Somatic Cancer Tissue Mutations in Plasma Cell-Free DNA for Predicting Disease State and Patient Survival

Varkalaitė

Förster

Franke

et al. 2021

Clin Transl Gastroenterol

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Introduction: Gastric cancer (GC) diagnosis in late stages and high mortality rates are the main issues that require new noninvasive molecular tools. We aimed to assess somatic mutational profiles in GC tissue and plasma cell-free DNA (cfDNA), evaluate their concordance rate, and analyze the role of multilayer molecular profiling to predict disease state and prognosis. Methods: Treatment-naive GC patient group (n = 29) was selected. Whole exome sequencing (WES) of GC tissue was performed, and a unique 38-gene panel for deep targeted sequencing of plasma cfDNA was developed. Oncoproteins were measured by enzyme-linked immunosorbent assay, and other variables such as tumor mutational burden and microsatellite instability were evaluated using WES data. Results: The yield of cfDNA was increased 43.6-fold; the integrity of fragments was decreased in GC compared with controls. WES analysis of cancerous tissue and plasma cfDNA (targeted sequencing) mutational profiles revealed 47.8% concordance. The increased quantity of GC tissue–derived alterations detected in cfDNA was associated with worse patients' survival. Analysis of importance of multilayer variables and receiver operating characteristic curve showed that combination of 2 analytes: (i) quantity of tissue matching alterations and (ii) presence of any somatic alteration in plasma cfDNA resulted in area under curve 0.744 when discriminating patients with or without distant metastasis. Furthermore, cfDNA sequence alterations derived from tumor tissue were detected in patients who had even relatively small GC tumors (T1-T2). Discussion: Our results indicate that quantitative and qualitative cfDNA mutational profile analysis is a promising tool for evaluating GC disease status or poorer prognosis.

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Section: Introductionmentioning

confidence: 99%

Liquid Biopsy in Gastric Cancer: Analysis of Somatic Cancer Tissue Mutations in Plasma Cell-Free DNA for Predicting Disease State and Patient Survival

Varkalaitė

Förster

Franke

et al. 2021

Clin Transl Gastroenterol

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“…Although still few, some fundamental studies in mice were performed in a prospective manner to guide clinical treatment decisions [76,[94][95][96][97]. In 2014, Stebbing et al [95] established 16 mPDXs from 29 patients with advanced sarcoma.…”

Section: Correlation Of Drug Response With Matched Patient Treatment mentioning

confidence: 99%

“…Despite limitations in efficiency, speed and cost, Avatars proved to be useful at tailoring therapy in 5 patients [95]. More recently, Mahecha and colleagues established a mPDX model from a metastatic HER2 + gastric cancer patient and tested ado-trastuzumab emtansine as an alternative therapy for the patient, who responded to treatment before relapsing 6 months later [97]. Results from mouse Avatars generally take months to be available.…”

Section: Correlation Of Drug Response With Matched Patient Treatment mentioning

confidence: 99%

Zebrafish Avatars towards Personalized Medicine—A Comparative Review between Avatar Models

Costa

Estrada

Mendes

et al. 2020

Cells

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Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average response rates. "Omics" approaches are used for patient stratification and choice of therapeutic options towards a more precise medicine. These methods, however, do not consider all genetic and non-genetic dynamic interactions that occur upon drug treatment. Therefore, the need to directly challenge patient cells in a personalized manner remains. The present review addresses the state of the art of patient-derived in vitro and in vivo models, from organoids to mouse and zebrafish Avatars. The predictive power of each model based on the retrospective correlation with the patient clinical outcome will be considered. Finally, the review is focused on the emerging zebrafish Avatars and their unique characteristics allowing a fast analysis of local and systemic effects of drug treatments at the single-cell level. We also address the technical challenges that the field has yet to overcome.The arrival of precision medicine and immunotherapy are giving hope to finally manage cancer treatment. Many advances were made possible due to the discovery of molecular pathways in tumor cells and on their interaction with the surrounding tumor microenvironment (TME) [1], leading to the development of many new therapies. The latest successes in HER2-targeted therapy and the discovery of immune checkpoint inhibitors are great examples of this [2]. However, not all patients respond and many are not eligible for these "new therapies". Thus, nowadays, the majority of patients are still treated with traditional chemo/radiotherapy and surgery according to clinical guidelines, which are developed and approved based on average efficacy rates.As a result of this "one-size-fits-all" approach, treatments may prove to be efficient for some patients but not for others. For example, in the international therapeutic guidelines (NCCN and ESMO) for advanced colorectal cancer (CRC) there are two main chemotherapeutic arms (FOLFOX and FOLFIRI), which show very similar response rates of~50% [3,4]. In other words,~50% of patients respond to treatment while~50% do not. Clinicians do not know in which group patients will fall, as there is no predictive screening test to provide this information. Thus, patients that start with FOLFOX and do not respond change to FOLFIRI, and vice-versa. This applies for CRC and many other cancers, being especially relevant in the metastatic scenario when oncology therapy guidelines reach branch

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“…ctDNA can be used for HER2-targeted population screening, since there is a high concordance of HER2 amplification between ctDNA and tumor tissues ( 52 , 53 ). Also, HER2 CNV detected in ctDNA could be used to monitor trastuzumab efficacy ( 52 , 54 , 55 ), as well as to predict innate trastuzumab resistance ( 54 ) and the developed one ( 43 ).…”

Section: Clinical Utility Of Ctdnamentioning

confidence: 99%

Clinical Applications of Liquid Biopsy in Gastric Cancer

Chivu‐Economescu¹,

Necula²,

Matei³

et al. 2021

Front. Med.

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Liquid biopsy represents an exciting new area in the field of cancer diagnosis and management, offering a less invasive and more convenient approach to obtain a time-point image of the tumor burden and its genomic profile. Samples collected from several body fluids, mostly blood, can be used to gain access to circulating tumor cells and DNA, non-coding RNAs, microRNAs, and exosomes, at any moment, offering a dynamic picture of the tumor. For patients with GC, the use of blood-based biopsies may be particularly beneficial since tissue biopsies are difficult to obtain and cause real distress to the patient. With advantages such as repeatability and minimal invasion, it is no wonder that the field of liquid biopsy has received tremendous attention. However, the abundance of studies, involving a wide range of assays with different principles, prevented for the moment the reproducibility of the results and therefore the translation into the clinic of liquid biopsy. In this review, we present the latest technical development and data on circulating biomarkers available through liquid biopsy in gastric cancer with an emphasis on their clinical utility in areas such as cancer screening, prognostic stratification, and therapeutic management.

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Precision Medicine Tools to Guide Therapy and Monitor Response to Treatment in a HER-2+ Gastric Cancer Patient: Case Report

Cited by 8 publications

References 33 publications

Liquid Biopsy in Gastric Cancer: Analysis of Somatic Cancer Tissue Mutations in Plasma Cell-Free DNA for Predicting Disease State and Patient Survival

Liquid Biopsy in Gastric Cancer: Analysis of Somatic Cancer Tissue Mutations in Plasma Cell-Free DNA for Predicting Disease State and Patient Survival

Zebrafish Avatars towards Personalized Medicine—A Comparative Review between Avatar Models

Clinical Applications of Liquid Biopsy in Gastric Cancer

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