scholarly journals Androgen receptor gain in circulating free DNA and splicing variant 7 in exosomes predict clinical outcome in CRPC patients treated with abiraterone and enzalutamide

2021 ◽  
Author(s):  
M. Del Re ◽  
V. Conteduca ◽  
S. Crucitta ◽  
G. Gurioli ◽  
C. Casadei ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Clinical Outcome ◽  
Liquid Biopsy ◽  
Response To Treatment ◽  
First Line ◽  
Primary Resistance ◽  
Circulating Free Dna ◽  
Free Dna ◽  
Signaling Inhibitors

Abstract Background Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the role of AR in liquid biopsy to predict clinical outcome to AR signaling inhibitors in mCRPC patients. Methods Six milliliters of plasma samples were collected before first-line treatment with abiraterone or enzalutamide. Circulating free DNA (cfDNA) and exosome-RNA were isolated for analysis of AR gain and AR splice variant 7 (AR-V7), respectively, by digital droplet PCR. Results Eighty-four mCRPC patients received abiraterone (n = 40) or enzalutamide (n = 44) as first-line therapy. Twelve patients (14.3%) presented AR gain and 30 (35.7%) AR-V7+ at baseline. Median progression-free survival (PFS) and overall survival (OS) were significantly longer in AR-V7− vs AR-V7+ patients (24.3 vs 5.4 months, p < 0.0001; not reached vs 16.2 months, p = 0.0001, respectively). Patients carrying the AR gain had a median PFS of 4.8 vs 24.3 months for AR normal patients (p < 0.0001). Median OS was significantly longer in AR normal vs patients with AR gain (not reached vs 8.17 months, p < 0.0001). A significant correlation between AR-V7 and AR gain was observed (r = 0.28; p = 0.01). The AR gain/AR-V7 combined analysis confirmed a strong predictive effect for biomarkers combination vs patients without any AR aberration (PFS 3.8 vs 28 month, respectively; OS 6.1 vs not reached, respectively; p < 0.0001). Conclusions The present study demonstrates that cfDNA and exosome-RNA are both a reliable source of AR variants and their combined detection in liquid biopsy predicts resistance to AR signaling inhibitors.

scholarly journals Cell-free DNA in non-small cell lung cancer

2017 ◽  
Vol 24 (2) ◽  
pp. 138-144 ◽  
Author(s):  
Vaida Gedvilaitė ◽  
Diana Schveigert ◽  
Saulius Cicėnas
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Response To Treatment ◽  
Small Cell Lung ◽  
Circulating Free Dna ◽  
Free Dna

Lung cancer is the leading cause of cancer-associated deaths worldwide. Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC). Advances in the knowledge of the biology of non-small cell lung cancer have revealed molecular information used for systemic cancer therapy targeting metastatic disease, with an important impact on patients’ overall survival (OS) and quality of life. However, a biopsy of overt metastases is an invasive procedure limited to certain locations and not easily acceptable in the clinic. The analysis of peripheral blood samples of cancer patients represents a new source of cancer-derived material, known as liquid biopsy, and its components (circulating tumour cells (CTCS), circulating free DNA (cfDNA), exosomes, and tumour-educated platelets (TEP)) can be obtained from almost any body fluids. These components have shown to reflect characteristics of the status of both the primary and metastatic diseases, helping the clinicians to move towards a personalized medicine (1). This review focuses on the liquid biopsy component – circulating free DNA, its benefit for non-invasive screening, early diagnosis, prognosis, response to treatment, and real time monitoring of the disease in non-small cell lung cancer patients.

The Role of Cell-Free Plasma DNA in Critically Ill Patients with Sepsis

2015 ◽  
Vol 41 (1-3) ◽  
pp. 34-40 ◽  
Author(s):  
Anna Clementi ◽  
Grazia Maria Virzì ◽  
Alessandra Brocca ◽  
Silvia Pastori ◽  
Massimo de Cal ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Prognostic Marker ◽  
Caspase 3 ◽  
Fungal Infections ◽  
Kidney Injury ◽  
Response To Treatment ◽  
Outcome Predictors ◽  
Plasma Dna ◽  
Free Plasma

Background: The identification of highly reliable outcome predictors in severe sepsis is important to define disease severity, predict bedside prognosis and monitor response to treatment. Cell-free plasma DNA (cfDNA) has been recently proposed as a possible prognostic marker of clinical outcome in septic patients. In this study, we investigated the prognostic value of cfDNA in patients with sepsis and its possible correlation with caspase-3, IL-6 and IL-18 levels. Methods: We enrolled 34 patients admitted to the intensive care unit (ICU). Out of these 34, 27 patients were septic and 7 were non-septic. cfDNA was extracted from plasma and quantified by real time PCR. Plasma levels of caspase-3, IL-6 and IL-18 were measured by ELISA. Results: We observed significantly higher levels of cfDNA in septic patients. No significant differences were found between cfDNA levels in patients with Gram+, Gram- and fungal infections. Out of the 27 septic patients, 12 developed acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), and cfDNA levels resulted to be higher in this group. Out of the 27 septic patients, 11 had a negative outcome during the ICU stay. The cfDNA concentrations at admission were higher in non-survivors than in survivors. Caspase-3, IL-6 and IL-18 levels were significantly higher in septic patients when compared to these levels in non-septic patients and correlated with cfDNA levels. Conclusion: cfDNA can be considered a good prognostic marker of clinical outcome in septic patients. Its levels increase in case of AKI complicating sepsis, in particular if CRRT is needed, and are associated with poor outcome. Caspase-3, IL-6 and IL-18 levels are higher in septic patients and correlate to cfDNA concentrations.

Assessment of immunohistochemical testing for androgen receptor splice variant 7 as a biomarker to predict resistance to androgen receptor signaling inhibitors in metastatic prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 308-308
Author(s):  
Ojas Harihar Vyas ◽  
Matthew James Butler ◽  
Elizabeth Ann Bowhay-Carnes ◽  
Muhammad Pathan ◽  
Paromita Datta
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Splice Variant ◽  
Receptor Signaling ◽  
Health Administration ◽  
Primary Resistance ◽  
Androgen Receptor Signaling ◽  
Signaling Inhibitors ◽  
Psa Response ◽  
Androgen Receptor Splice Variant

308 Background: Androgen receptor splice variant 7 (AR-V7) has been shown to confer resistance to androgen receptor signaling inhibitors (ARS-I) such as enzalutamide (enza) and abiraterone (abi). Resistance can be observed at the time of initial treatment, or may be acquired later in the disease course. Prior research has primarily focused on AR-V7 expression in circulating tumor cells (CTCs) but the utility of more affordable immunohistochemical (IHC) testing to predict for primary resistance to ARS-I remains unknown, which is of particular relevance as ARS-I gain use as initial therapy. Methods: We identified patients in the South Texas Veterans Health Administration Tumor Registry with metastatic, castrate-resistant prostate cancer who received ARS-I since 2011. IHC for AR-V7 staining was validated on controls and performed on tissue from the most recent tissue specimen (diagnostic biopsy, prostatectomy, or biopsy of a metastatic site) on all identified patients with adequate tissue available. Results: 25 of 42 (60%) patients receiving abi had PSA response with median duration of response (DOR) of 231 days. 14 of 26 (54%) of patients receiving enza experienced PSA response with a median DOR of 165 days. IHC is currently being interpreted on stored tissue specimens to assess predictive efficacy of AR-V7 staining. The de-novo rate of AR-V7 expression and correlation with response to ARS-I in the veteran population will be reported with final results. Conclusions: IHC testing for AR-V7 may provide a cost-effective biomarker to identify patients resistant to ARS-I, thus avoiding thus avoiding time-consuming and costly treatment with ineffective therapy. Further study is warranted to assess cost-effectiveness and reduction in unnecessary toxicity by the use of IHC testing for AR-V7 in the front-line setting to predict primary resistance for patients that would otherwise qualify for ARS-I.

The role of circulating free DNA in the management of NSCLC

2018 ◽  
Vol 19 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Riziero Esposito Abate ◽  
Raffaella Pasquale ◽  
Francesca Fenizia ◽  
Anna Maria Rachiglio ◽  
Cristin Roma ◽  
...  
Keyword(s):  
Circulating Free Dna ◽  
Free Dna

scholarly journals Investigation of appropriate pre-analytical procedure for circulating free DNA from liquid biopsy

Oncotarget ◽  
2018 ◽  
Vol 9 (61) ◽  
pp. 31904-31914 ◽  
Author(s):  
Akemi Sato ◽  
Chiho Nakashima ◽  
Tomonori Abe ◽  
Junichi Kato ◽  
Mitsuharu Hirai ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Analytical Procedure ◽  
Circulating Free Dna ◽  
Free Dna

PROX: Primary resistance to oxaliplatin containing regimen in the first line treatment of metastatic colorectal carcinoma—Retrospective analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 855-855
Author(s):  
Larissa Machado ◽  
Tiago Felismino ◽  
Diogo De Brito Sales ◽  
Diogo Morbeck ◽  
Amanda Karani ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
Progression Free Survival ◽  
First Line ◽  
Primary Resistance ◽  
Free Survival ◽  
Mucinous Component ◽  
First Response ◽  
Single Center Study ◽  
Third Line

855 Background: The rate of primary resistance to modern first line (FL) chemotherapy regimen in the treatment of metastatic colorectal cancer (mCRC) is low. Progression Disease (PD) to FOLFOX in the FL is less than 15% in most trials. Prognostic factors associated with worse outcome in mCRC have been identified. However, primary resistance to Oxaliplatin (PROX) containing regimen is not well understood, as well as the role of salvage therapy in further lines of treatment. The aim of the study was to analyze clinical and pathological characteristics of patients with PROX. Methods: A retrospective, single center study included patients that presented PD in the first response evaluation with an Oxaliplatin containing regimen in the FL treatment of mCRC. We also evaluated the Overall Survival (OS) and progression free survival (PFS) of these patients to second and third line. Clinical and pathological variables were analyzed and correlated with (OS). Results: A total of 55 patients were inclued. Median age these cohort was 57 years. Female/Male rate was 42%/58%. Mucinous component was 27%. Right and Left colon was 27% and 66%, respectively. BRAF mutation (2/16 pts). Wild type KRAS was 44%. Synchronic metastasis was 75%. Ressection of metastasis was performed in 20%. Liver limeted disease was found in 45%. Main chemotherapy regimen containing oxaliplatin was FOLFOX (78%) in first line. Bevacizumab, Cetuximab and Panitumumab were used in 21.8%, 9%, 1.8%, respectively. OS was 9.4 months. PFS in second line 3.8 months (47 pts) and third line 3.5 months (18 pts). The only variable associated with longer survival was resection of metastasis (25.6 x 8.6 months, p=0.039). Conclusions: No clinical and pathological variable were able to predict primary resistance to Oxaliplatin containing regimen. However, we found a higher proportion of mucinous subtype. Patients submitted to resection of metastasis had almost three fold the survival of patient that did not underwent surgery. Refractory patients have a very short survival. Further lines of treatment are not able to rescue these patients. Further studies focusing in patients with primary resistance to chemotherapy in first line are needed.

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