scholarly journals Molecular Characterization of Prostate Cancers in the Precision Medicine Era

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4771
Author(s):  
Emilio Francesco Giunta ◽  
Laura Annaratone ◽  
Enrico Bollito ◽  
Francesco Porpiglia ◽  
Matteo Cereda ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Circulating Tumor Dna ◽  
Molecular Tests ◽  
Repair Deficiency ◽  
Metastatic Setting ◽  
Pros And Cons ◽  
Prostate Cancers ◽  
Optimal Therapeutic Strategy ◽  
Pathway Deregulation

Prostate cancer (PCa) therapy has been recently revolutionized by the approval of new therapeutic agents in the metastatic setting. However, the optimal therapeutic strategy in such patients should be individualized in the light of prognostic and predictive molecular factors, which have been recently studied: androgen receptor (AR) alterations, PTEN-PI3K-AKT pathway deregulation, homologous recombination deficiency (HRD), mismatch repair deficiency (MMRd), and tumor microenvironment (TME) modifications. In this review, we highlighted the clinical impact of prognostic and predictive molecular factors in PCa patients’ outcomes, identifying biologically distinct subtypes. We further analyzed the relevant methods to detect these factors, both on tissue, i.e., immunohistochemistry (IHC) and molecular tests, and blood, i.e., analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Moreover, we discussed the main pros and cons of such techniques, depicting their present and future roles in PCa management, throughout the precision medicine era.

scholarly journals Towards Circulating-Tumor DNA-Based Precision Medicine

2019 ◽  
Vol 8 (9) ◽  
pp. 1365 ◽  
Author(s):  
Ai Hironaka-Mitsuhashi ◽  
Anna Sanchez Calle ◽  
Takahiro Ochiya ◽  
Shin Takayama ◽  
Akihiko Suto
Keyword(s):  
Decision Making ◽  
Precision Medicine ◽  
Clonal Evolution ◽  
Predictive Biomarkers ◽  
Circulating Tumor Dna ◽  
Response To Therapy ◽  
Molecular Characteristics ◽  
Cancer Management ◽  
Cancer Breast ◽  
Metastatic Setting

In the era of precision medicine, targeted therapies have been implemented for various diseases. Genomic information guides decision-making in cancer treatment. The improvements in next-generation sequencing and polymerase chain reaction have made it possible to access the genetic information using circulating-tumor DNAs (ctDNAs). Molecular characteristics of individual tumors can be obtained by analysis of ctDNAs, thus making them excellent tools to guide decision-making during treatment. In oncology, the use of ctDNAs in clinical practice is now gaining importance. Molecular analysis of ctDNAs has potential for multiple clinical applications, including early diagnosis, prognosis of disease, prognostic and/or predictive biomarkers, and monitoring response to therapy and clonal evolution. In this paper, we highlight the applications of ctDNAs in cancer management, especially in metastatic setting, and summarize recent studies about the use of ctDNAs as predictive biomarkers for the therapeutic adaptation/response in lung cancer, breast cancer, and colorectal cancer. These studies offer the evidence to use ctDNAs as a promising approach to solve unmet clinical needs.

scholarly journals The interplay of Clostridioides difficile infection and inflammatory bowel disease

2021 ◽  
Vol 14 ◽  
pp. 175628482110202
Author(s):  
Kanika Sehgal ◽  
Devvrat Yadav ◽  
Sahil Khanna
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Adverse Outcomes ◽  
Molecular Tests ◽  
Clostridioides Difficile ◽  
Increased Risk ◽  
Clostridioides Difficile Infection ◽  
Pros And Cons ◽  
Inflammatory Bowel ◽  
High Index Of Suspicion

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

scholarly journals Heterogeneous constitutional mismatch repair deficiency with MSH6 missense mutation clinically benefits from pembrolizumab and regorafenib combination therapy: a case report and literature review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Xie ◽  
Qin Feng ◽  
Zhongwu Li ◽  
Ming Lu ◽  
Jian Li ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Dual Therapy ◽  
Circulating Tumor Dna ◽  
Targeted Sequencing ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Mutation Burden

Abstract Background Germline DNA mismatch repair (MMR) gene aberrations are associated with colorectal cancer (CRC) predisposition and high tumor mutation burden (TMB-H), with increased likelihood of favorable response to immune checkpoint inhibitors (ICIs). Case presentation We present a 32-year old male patient diagnosed with constitutional MMR deficiency (CMMRD) CRC whose MMR immunohistochemistry (IHC) revealed inconsistent results from two tumor blocks. Targeted sequencing of two tumor specimens used in MMR-IHC and plasma-derived circulating tumor DNA consistently revealed the detection of bi-allelic germline MSH6 c.3226C > T (p.R1076C) mutation, TMB-H as well as the genetic heterogeneity of the tumor samples. Unexpectedly, both blocks were microsatellite stable (MSS) after PCR confirmation. Interestingly, the patient failed to show response to ICI monotherapy or dual therapy, but clinically benefitted from combined therapy of ICI pembrolizumab plus multi-kinase inhibitor regorafenib. Conclusion Our case reported a CMMRD patient with heterogeneous MMR results who showed complicated response to ICIs, highlighting the importance of accurate diagnosis using targeted sequencing with multiple specimens to reveal the possible mechanism of response to ICI in patients with CMMRD.

Use of Circulating Cell-Free DNA to Guide Precision Medicine in Patients with Colorectal Cancer

2021 ◽  
Vol 72 (1) ◽  
pp. 399-413
Author(s):  
Van K. Morris ◽  
John H. Strickler
Keyword(s):  
Colorectal Cancer ◽  
Precision Medicine ◽  
Residual Disease ◽  
Cost Effective ◽  
Patient Specific ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Metastatic Setting ◽  
Diagnostic Technology

Patient-specific biomarkers form the foundation of precision medicine strategies. To realize the promise of precision medicine in patients with colorectal cancer (CRC), access to cost-effective, convenient, and safe assays is critical. Improvements in diagnostic technology have enabled ultrasensitive and specific assays to identify cell-free DNA (cfDNA) from a routine blood draw. Clinicians are already employing these minimally invasive assays to identify drivers of therapeutic resistance and measure genomic heterogeneity, particularly when tumor tissue is difficult to access or serial sampling is necessary. As cfDNA diagnostic technology continues to improve, more innovative applications are anticipated. In this review, we focus on four clinical applications for cfDNA analysis in the management of CRC: detecting minimal residual disease, monitoring treatment response in the metastatic setting, identifying drivers of treatment sensitivity and resistance, and guiding therapeutic strategies to overcome resistance.

Circulating tumor DNA mutation as a prognostic marker in melanoma with brain metastasis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21560-e21560
Author(s):  
Tapas Ranjan Behera ◽  
Jung Min Song ◽  
Donald Matthew Eicher ◽  
Brian Gastman ◽  
Daniel H. Farkas ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Metastatic Disease ◽  
Braf Mutation ◽  
Mutation Detection ◽  
Objective Response ◽  
Unmet Need ◽  
Circulating Tumor Dna ◽  
Metastatic Setting ◽  
Tumor Dna

e21560 Background: Prognosis in melanoma with brain metastasis is poor with a median survival of four months and a one-year survival rate of 10–20%. There is an unmet need for surveillance methods that can supplement imaging at regular intervals. Serial analysis of circulating tumor DNA (ctDNA) may aid surveillance and prognostication. A PCR-based, “specimen in/result out” testing device was employed to detect BRAF variants in plasma-derived ctDNA to evaluate the utility of rapid biomarker detection in the management of melanoma with brain metastasis. Methods: Serial blood samples from patients diagnosed with BRAF mutation-positive metastatic melanoma were collected at regular intervals. We employed a real-time PCR-based automated mutation detection system (Idylla; Biocartis, Belgium) to interrogate the plasma samples. The ctDNA mutation detection trend was analyzed relative to disease progression. Results: 39 patients with BRAF mutation positive melanoma were enrolled. 29 patients were treated in the metastatic setting, 10 in the adjuvant setting. 18 of the 29 patients with metastatic disease (62%) had brain metastases. Circulating BRAF mutation was detected in 17 of the 29 (59%) patients with metastatic disease, and was not detected in any patients treated adjuvantly. In the group with metastatic disease, this circulating biomarker changed from undetectable to detectable in eight (28%) and detectable to undetectable in three (10%). No change in circulating mutation status occurred in 18 (62%). In the eight patients who had an initial negative test that later became positive, seven (87%) had brain metastases. In three patients, ctDNA mutation detection occurred before the diagnosis of brain metastases on imaging, with a median lead time of five weeks (range, 3-12 weeks). In one patient with de novo metastatic disease admitted to the ICU, tissue was unavailable for BRAF testing but plasma was found to be positive for ctDNA BRAF detection. BRAF/MEK targeted therapy resulted in a sustained objective response. Five of six (83%) patients that had persistent ctDNA positivity had brain metastases. Among patients with brain metastases, median overall survival (mOS) of patients demonstrating >50% test positivity was numerically longer than those with <50% positivity (mOS 12.3 vs 53.5 months; p = 0.133). Conclusions: Plasma-based, rapid ctDNA testing may be useful as an aid in detecting progression and gauging prognosis in patients with melanoma treated in the metastatic setting. The dynamics of ctDNA test positivity may indicate a need for more urgent imaging, particularly of the brain. Blood-based, semi-automated ctDNA detection may serve as an attractive adjunct to scheduled imaging surveillance in melanoma.

scholarly journals Diagnostic value of circulating tumor DNA in molecular characterization of glioma

Medicine ◽  
2020 ◽  
Vol 99 (33) ◽  
pp. e21196
Author(s):  
Yin Kang ◽  
Xiaohua Lin ◽  
Dezhi Kang
Keyword(s):  
Molecular Characterization ◽  
Diagnostic Value ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Prevalence of Extended-Spectrum β-Lactamases in E. coli of Rats in the Region North East of Gabon

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Richard Onanga ◽  
Pierre Philippe Mbehang Nguema ◽  
Guy Roger Ndong Atome ◽  
Arsène Mabika Mabika ◽  
Berthelemy Ngoubangoye ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
North East ◽  
Molecular Tests ◽  
Extended Spectrum ◽  
Susceptibility Tests ◽  
Animal Feces

Antibiotic resistance occurs in the environment by multiplication and the spread of multidrug-resistant bacteria that would be due to an improper and incorrect use of antibiotics in human and veterinary medicine. The aim of this study was to establish the prevalence of E.coli producing Extended-Spectrum beta-Lactamase (ESBL) antibiotics from rats and gregarious animals in a semirural area of Gabon and to evaluate the origin of a resistance distribution in the environment from animal feces. The bacterial culture was carried out, and the identification of E. coli strains on a specific medium and the antibiotic susceptibility tests allowed establishing the prevalence. Characterization of resistance genes was performed by gene amplification after DNA extraction. On 161 feces collected in rats, 32 strains were isolated, and 11 strains of E. coli produced ESBL with a prevalence of 34.37%. Molecular tests showed that CTX-M genes 214 bp were identified in rats. The presence of CTX-M genes could have a human origin. So, the rats can carry ESBL-producing Enterobacteriaceae which poses a risk to human health and pets in this region of Gabon.

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