scholarly journals Coupled liquid biopsy and bioinformatics for pancreatic cancer early detection and precision prognostication

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jun Hou ◽  
XueTao Li ◽  
Ke-Ping Xie

AbstractEarly detection and diagnosis are the key to successful clinical management of pancreatic cancer and improve the patient outcome. However, due to the absence of early symptoms and the aggressiveness of pancreatic cancer, its 5-year survival rate remains below 5 %. Compared to tissue samples, liquid biopsies are of particular interest in clinical settings with respect to minimal invasiveness, repeated sampling, complete representation of the entire or multi-site tumor bulks. The potential of liquid biopsies in pancreatic cancer has been demonstrated by many studies which prove that liquid biopsies are able to detect early emergency of pancreatic cancer cells, residual disease, and recurrence. More interestingly, they show potential to delineate the heterogeneity, spatial and temporal, of pancreatic cancer. However, the performance of liquid biopsies for the diagnosis varies largely across different studies depending of the technique employed and also the type and stage of the tumor. One approach to improve the detect performance of liquid biopsies is to intensively inspect circulome and to define integrated biomarkers which simultaneously profile circulating tumor cells and DNA, extracellular vesicles, and circulating DNA, or cell free DNA and proteins. Moreover, the diagnostic validity and accuracy of liquid biopsies still need to be comprehensively demonstrated and validated.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 824
Author(s):  
Felix I. L. Clanchy

Sarcomas are mesenchymal tumours that often arise and develop as a result of chromosomal translocations, and for several forms of sarcoma the EWSR1 gene is a frequent translocation partner. Sarcomas are a rare form of malignancy, which arguably have a proportionally greater societal burden that their prevalence would suggest, as they are more common in young people, with survivors prone to lifelong disability. For most forms of sarcoma, histological diagnosis is confirmed by molecular techniques such as FISH or RT-PCR. Surveillance after surgical excision, or ablation by radiation or chemotherapy, has remained relatively unchanged for decades, but recent developments in molecular biology have accelerated the progress towards routine analysis of liquid biopsies of peripheral blood. The potential to detect evidence of residual disease or metastasis in the blood has been demonstrated by several groups but remains unrealized as a routine diagnostic for relapse during remission, for disease monitoring during treatment, and for the detection of occult, residual disease at the end of therapy. An update is provided on research relevant to the improvement of the early detection of relapse in sarcomas with EWSR1-associated translocations, in the contexts of biology, diagnosis, and liquid biopsy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.


2020 ◽  
pp. 108-132
Author(s):  
Joseph Carmicheal ◽  
Rahat Jahan ◽  
Koelina Ganguly ◽  
Ashu Shah ◽  
Sukhwinder Kaur

Author(s):  
David Crosby

AbstractLiquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.


2012 ◽  
Vol 5 (5) ◽  
pp. 322-326
Author(s):  
Rei Suzuki ◽  
Hiromasa Ohira ◽  
Atsushi Irisawa ◽  
Manoop S. Bhutani

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14708-e14708
Author(s):  
William H. Sherman ◽  
Kyung Chu ◽  
John Allendorf ◽  
John A Chabot ◽  
Beth Schrope ◽  
...  

e14708 Background: When either gemcitabine (G) or capecitabine (X) are combined with RT, the median survival is less than 12 months. Approximately 30% of patients progress during the 9 week period of treatment and re-assessment. The benefit of RT in the post-op setting has been questioned. Co-administration of G and X is synergistic against pancreatic cancer cells and both are radiation sensitizers. They were combined with RT. Methods: A retrospective analysis was done on 48 patients treated with GTX (G, docetaxel (T) and X) followed by radiation therapy with concomitant G and X. RT was delivered by conformal fields or IMRT in 180 cGy fractions to 5040 cGy. X, 1,000 mg/m2 was given days 1 to 10 and days 16 to 25 of RT and G, 750 mg/m2 over 90 minutes, was given on days 5, 10, 20 and 25 of RT. The end-points were toxicity and local disease control. Results: 14 patients with positive margin of resection were treated adjuvantly and 34 patients with arterial involvement were treated neo-adjuvantly. No patient developed evidence of metastasis within the 9 weeks after starting RT. There were no bowel perforations, pancreatitis or delayed strictures. The therapy was well tolerated. Grade 3/4 toxicities were: thrombocytopenia 29%, leucopenia 38%, anemia 43%, enteritis 10% and infection 8%. 2 patients had GI bleeding from telangectasias more than 6 months after completing RT. The group of 14 treated adjuvantly had survival of 100% at 1 year, 86% at 2 years. 7 (57%) are beyond 3 years and have not relapsed. 34 patients treated neo-adjuvantly had one year survival of 85%. Of the 34 patients, 16 (47%) are alive with a median survival of 24 months (95% CI 20.7, 31.7.) 22 had resections with a median OS of 25.7 M (range 8.8 to 74.8 M.) 13 have not relapsed (13.6 to 74.8 M.) On pathology, there were 3 CR’s (14%,) 6 (27%) with scattered microscopic disease and 13 (59%) with macroscopic residual disease. Conclusions: G and X can be combined safely with radiation therapy to achieve local control of pancreatic cancer. Our results suggest that the aforementioned therapy, when combined with surgery, increases the long-term disease-free survival over results reported in the literature.


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