Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

Zhang, Cheng; Chen, Zuhua; Chong, Xiaoyi; Yang, Catherine F.; Wang, Zhenghang; Yu, Rong; Sun, Tingting; Chen, Xiaoxi; Shao, Yang; Zhang, Xiaotian; Gao, Jing; Shen, Lin

doi:10.1002/ctm2.254

Cited by 27 publications

(26 citation statements)

References 61 publications

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“…Thus, there is an unmet clinical need for a biomarker that more accurately reflects therapeutic efficacy and dynamic changes during therapy. Liquid biopsy, particularly ctDNA from plasma, has high sensitivity and specificity in early cancer detection ( 34 ), so it may be useful for assessing dynamic changes in genes. Furthermore, because tumor tissue sequencing often relies on archival tissue obtained prior to the development of metastatic disease, ctDNA profiling may more readily facilitate the analysis of patients with metastatic disease by better capturing the presence of tumor heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy

Yang

Zou

et al. 2022

Front. Oncol.

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BackgroundMetastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies.MethodsA single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed.ResultsWe conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072).ConclusionsThis study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy

Yang

Zou

et al. 2022

Front. Oncol.

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“…In different stages of its development, different components and genes participate in it. It is very beneficial for us to study gastric cancer better by studying various genes, mechanisms, and components involved in the development of GC [15,16]. In recent years, many studies have confirmed that miRNA almost participates in all cell biological processes, such as cell development, cell proliferation and apoptosis, cell migration, and invasion [17,18].…”

Section: Discussionmentioning

confidence: 99%

TP73-AS1 promotes gastric cancer proliferation and invasion by regulation miR-27b-3p/TMED5 axis

Bao¹,

Guo²

2022

J. Cancer

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Background: Gastric cancer (GC) is a common gastrointestinal malignancy. Evidence suggests that long non-coding RNAs (lncRNAs) influence mRNA expression to induce GC progression. We aim to investigate the function and regulatory mechanism of TP73-AS1 in GC. Materials and methods:We detected TP73-AS1, miR-27b-3p, and TMED5 (Transmembrane P24 Trafficking Protein 5) by real-time polymerase chain reaction (RT-PCR). Similarly, the protein levels of CRIM1 and wnt/β-catenin were detected by western-blot. The colony formation and Cell-Counting Kit-8 (CCK-8) assay detected cell proliferation. Transwell and scrape assay tested cell migration and invasion. Dual-luciferase reporter assays confirmed directed binding targets. Tumor xenograft in nude mice checked the result in vivo. Results: TP73-AS1 over-expressed in GC. Suppressed TP73-AS1 inhibited cell proliferation, migration, and invasion. However, down-regulated miR-424 could reverse the effects of weakenTP73-AS1 on the progression of GC. Moreover, TMED5 was also up-regulated in GC. Both TP73-AS1 and TMED5 were the direct target of miR-27b-3p. Meanwhile, miR-27b-3p was a negative correlation with TP73-AS1 and TMED5. The TP73-AS1/miR-27b-3p/TMED5 axis regulate wnt/β-catenin pathway. Conclusion: TP73-AS1 promoted GC proliferation, migration, and invasion by sponging miR-27b-3p to regulate TMED5. TP73-AS1 was a potential onco-lncRNA in GC.

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“…Additionally, ctDNA response could be used to evaluate therapeutic effect and to explore potential resistance mechanisms for targeted drugs (17,18). Considering the high heterogeneity characteristic of GC, ctDNA was used as an important tool for monitoring disease progression (19,20). The appearance of ctDNA could predict tumor recurrence earlier than routine imaging examination.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient

Li²,

Qin³

et al. 2022

Front. Oncol.

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BackgroundTrastuzumab plus chemotherapy remains the standard first-line treatment strategy for HER2-positive gastric cancer (GC). Trastuzumab resistance, on the other hand, remains a significant issue. There are a few effective anti-HER2 agents for patients who develop resistance to trastuzumab.Case PresentationA 49-year-old female was diagnosed with stage IV GC with liver and lung metastasis in July 2017. She underwent gastrostomy, and the immunohistochemistry (IHC) result of postoperative tissue demonstrated HER2 (3+). She received first-line treatment of trastuzumab (440 mg), oxaliplatin (200 mg), and S-1 (40 mg). After treatment for 6 months, the patient achieved complete response (CR) with PFS up to 21 months. After progression, she subsequently received trastuzumab (440 mg) plus oxaliplatin (200 mg) as second-line treatment. However, the patient developed resistance to trastuzumab after 12 months of treatment. She started to receive third-line treatment of irinotecan (200 mg d1) and capecitabine (60 mg bid) plus pyrotinib (400 mg/day). After 2 months of treatment, the tumor is evaluated as partial response with PFS of 12 months.ConclusionsWe presented a patient with HER2-positive GC who benefited from the pyrotinib-based treatment after two lines of trastuzumab-based therapies failed. Further research is required to validate such conclusions.

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Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies

Cited by 27 publications

References 61 publications

Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy

Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy

TP73-AS1 promotes gastric cancer proliferation and invasion by regulation miR-27b-3p/TMED5 axis

Case Report: Durable Clinical Response to Third-Line Pyrotinib After Resistance to Trastuzumab in a Gastric Cancer Patient

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