scholarly journals Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87221-87233 ◽  
Author(s):  
Patricia Adamo ◽  
Caroline M. Cowley ◽  
Christopher P. Neal ◽  
Vilas Mistry ◽  
Karen Page ◽  
...  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyung Sun Kim ◽  
Young Jae Kim ◽  
Kwang Gi Kim ◽  
Joon Seong Park

AbstractPancreatic cancer is a lethal disease, and resistance to chemotherapy is a critical factor influencing the postoperative prognosis. Tumour heterogeneity is an important indicator of chemoresistance. Therefore, we analysed tumour heterogeneity in preoperative computed tomography scans by performing texture analysis using the grey-level run-length matrix and analysed the correlation of survival with the value obtained in these analyses. We analysed 116 consecutive patients who underwent curative resection and had preoperative contrast-enhanced computed tomography data available for analysis. A region of interest was drawn on all slices with a visible tumour and normal pancreas on the arterial phase computed tomography scans; the correlation of pathological characteristics with grey-level run-length matrix features was analysed. We then performed Kaplan–Meier survival curve analysis among pancreatic cancer patients. The grey-level non-uniformity values in grey-level run-length matrix features for tumours were higher than those for normal pancreas. High grey-level non-uniformity values represent a non-uniform texture, i.e., heterogeneity. Grey-level run-length matrix features showed that recurrence-free survival was shorter in the group with high grey-level non-uniformity 135 values (p = 0.025). Our analyses of the correlation between pathological outcomes and grey-level run-length matrix features in pancreatic cancer patients showed that grey-level non-uniformity values were powerful prognostic indicators.


2016 ◽  
Vol 115 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Naoto Hadano ◽  
Yoshiaki Murakami ◽  
Kenichiro Uemura ◽  
Yasusi Hashimoto ◽  
Naru Kondo ◽  
...  

2018 ◽  
Vol 19 (8) ◽  
pp. 2311 ◽  
Author(s):  
Laura Muinelo-Romay ◽  
Carlos Casas-Arozamena ◽  
Miguel Abal

The identification of new molecular targets and biomarkers associated with high risk of recurrence and response to therapy represents one of the main clinical challenges in the management of advanced disease in endometrial cancer. In this sense, the field of liquid biopsy has emerged as a great revolution in oncology and is considered “the way” to reach personalised medicine. In this review, we discuss the promising but already relatively limited advances of liquid biopsy in endometrial cancer compared to other types of tumours like breast, colorectal or prostate cancer. We present recent data analysing circulating tumour material in minimally-invasive blood samples, but also in alternative forms of liquid biopsy like uterine aspirates. Proteomic and genomic studies focused on liquid-based uterine samples are resulting not only in optimal diagnostic tools but also in reliable approaches to address tumour heterogeneity. Likewise, circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) represent an opportunity for the correct stratification of patients, for the assessment of early recurrent disease or for the real-time monitoring of therapy responses. Appropriately designed studies and implementation in clinical trials will determine the value of liquid biopsy for precision oncology in endometrial cancer.


2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Stefania Forciniti ◽  
Marta Cavo ◽  
Ilaria Dando ◽  
Elisa Dalla Pozza ◽  
Marta Palmieri ◽  
...  

In this study we produced 3D organotypic cultures and spheroids to mimic the complex microenvironment of pancreatic cancer and to test alternative therapeutic strategies.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Jacob J. Chabon ◽  
Andrew D. Simmons ◽  
Alexander F. Lovejoy ◽  
Mohammad S. Esfahani ◽  
Aaron M. Newman ◽  
...  

Abstract Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of patients after treatment with first-line inhibitors, indicating frequent intra-patient heterogeneity. Rociletinib resistance recurrently involves MET, EGFR, PIK3CA, ERRB2, KRAS and RB1. We describe a novel EGFR L798I mutation and find that EGFR C797S, which arises in ∼33% of patients after osimertinib treatment, occurs in <3% after rociletinib. Increased MET copy number is the most frequent rociletinib resistance mechanism in this cohort and patients with multiple pre-existing mechanisms (T790M and MET) experience inferior responses. Similarly, rociletinib-resistant xenografts develop MET amplification that can be overcome with the MET inhibitor crizotinib. These results underscore the importance of tumour heterogeneity in NSCLC and the utility of ctDNA-based resistance mechanism assessment.


Sign in / Sign up

Export Citation Format

Share Document