scholarly journals Liquid biopsy in lung cancer: tertiary prevention potential

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
F Rubba ◽  
F Pepe ◽  
R Martello ◽  
R Egidio ◽  
T De Pascale ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Laboratory Data ◽  
Resistance Mutation ◽  
Tertiary Prevention ◽  
Specific Gene ◽  
Screening Designs ◽  
Molecular Features ◽  
Diagnostic Potential

Abstract Background In the era of personalized therapy liquid biopsy is considered an important diagnostic tool in the clinical management of cancer patients. Tissue specimen represents “gold standard” for molecular evaluation of specific gene targets alterations that lead cancer patients to benefit of a “tailed therapy” based on molecular features of the tumor. This innovative source of nucleic acids was introduced in clinical setting only for NSCLC patients to test Epidermal Grow Factor Receptor (EGFR) mutations when tissue is not available or to monitor acquired resistance mutation after a first line of treatment. The study aimed at assessing the diagnostic potential of liquid biopsy in balanced tertiary screening modeling. Methods The cases relating to 5 years of activity regarding to molecular diagnostics performed on liquid biopsy specimens in the Predictive Diagnostic laboratory of AOU Federico II were reviewed. Laboratory data were collected in SPSS. Non parametric analysis were performed in order to test the differences between patients WILD TYPE or not. A multivariate logistic model was performed in order to assess the effect of mutation, age and sex, on the tumor progression. The results of the revision concern 515 total cases (almost of all plasma or peripheral blood) allowed to evaluate the liquid biopsies for women and men. The average age of the Patients is 66.3 years, and the 25 percentile is 59 years. Results The cases are 221 basal and 294 by progression. The cases with mutation, as expected, have an OR 4,15 compared to the basal to have a tumor progression (95% IC: 2,7 - 6,3) regardless of sex and age. The mutations detected were 131 from different types of pulmonary carcinomas. Conclusions Working on case data, specifying the characteristics of the Patients with mutations will drive a further estimate in tertiary prevention screening designs. Key messages In the last five years, the liquid biopsy has been used for different purposes in oncology. To specify the characteristics of the Patients with mutations will drive a further estimate in tertiary prevention screening designs.

scholarly journals Droplet Digital PCR Analysis of Liquid Biopsy Samples Unveils the Diagnostic Role of hsa-miR-133a-3p and hsa-miR-375-3p in Oral Cancer

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 379
Author(s):  
Salvatore Crimi ◽  
Luca Falzone ◽  
Giuseppe Gattuso ◽  
Caterina Maria Grillo ◽  
Saverio Candido ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Pcr Analysis ◽  
Screening Programs ◽  
Diagnostic Potential ◽  
Oral Cancer Patients

Despite the availability of screening programs, oral cancer deaths are increasing due to the lack of diagnostic biomarkers leading to late diagnosis and a poor prognosis. Therefore, there is an urgent need to discover novel effective biomarkers for this tumor. On these bases, the aim of this study was to validate the diagnostic potential of microRNAs (miRNAs) through the analysis of liquid biopsy samples obtained from ten oral cancer patients and ten healthy controls. The expression of four selected miRNAs was evaluated by using droplet digital PCR (ddPCR) in a pilot cohort of ten oral cancer patients and ten healthy donors. Bioinformatics analyses were performed to assess the functional role of these miRNAs. The expression levels of the predicted down-regulated hsa-miR-133a-3p and hsa-miR-375-3p were significantly reduced in oral cancer patients compared to normal individuals while no significant results were obtained for the up-regulated hsa-miR-503-5p and hsa-miR-196a-5p. ROC analysis confirmed the high sensitivity and specificity of hsa-miR-375-3p and hsa-miR-133a-3p. Therefore, both miRNAs are significantly down-regulated in cancer patients and can be used as biomarkers for the early diagnosis of oral cancer. The analysis of circulating miRNAs in a larger series of patients is mandatory to confirm the results obtained in this pilot study.

Cancer Biomarker Discovery for Precision Medicine: New Progress

2020 ◽  
Vol 26 (42) ◽  
pp. 7655-7671 ◽  
Author(s):  
Jinfeng Zou ◽  
Edwin Wang
Keyword(s):  
Precision Medicine ◽  
Cancer Patients ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Biomarker Discovery ◽  
Deep Understanding ◽  
Genetic Mutation ◽  
Data Driven ◽  
Novel Approaches ◽  
Functional Biomarkers

Background: Precision medicine puts forward customized healthcare for cancer patients. An important way to accomplish this task is to stratify patients into those who may respond to a treatment and those who may not. For this purpose, diagnostic and prognostic biomarkers have been pursued. Objective: This review focuses on novel approaches and concepts of exploring biomarker discovery under the circumstances that technologies are developed, and data are accumulated for precision medicine. Results: The traditional mechanism-driven functional biomarkers have the advantage of actionable insights, while data-driven computational biomarkers can fulfill more needs, especially with tremendous data on the molecules of different layers (e.g. genetic mutation, mRNA, protein etc.) which are accumulated based on a plenty of technologies. Besides, the technology-driven liquid biopsy biomarker is very promising to improve patients’ survival. The developments of biomarker discovery on these aspects are promoting the understanding of cancer, helping the stratification of patients and improving patients’ survival. Conclusion: Current developments on mechanisms-, data- and technology-driven biomarker discovery are achieving the aim of precision medicine and promoting the clinical application of biomarkers. Meanwhile, the complexity of cancer requires more effective biomarkers, which could be accomplished by a comprehensive integration of multiple types of biomarkers together with a deep understanding of cancer.

scholarly journals Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlos Henrique F. Peiró ◽  
Matheus M. Perez ◽  
Glauco S. A. de Aquino ◽  
Jéssica F. A. Encinas ◽  
Luiz Vinícius de A. Sousa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Glucose Transporter ◽  
Carbonic Anhydrases ◽  
Breast Cancer Patients ◽  
Gene Expressions ◽  
Liquid Biopsies ◽  
Healthy Women ◽  
Diagnostic Potential ◽  
Laboratory Tool

AbstractIn tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.

scholarly journals Cell Fitness: More Than Push-Ups

2021 ◽  
Vol 22 (2) ◽  
pp. 518
Author(s):  
Adam James Ferrari ◽  
Ronny Drapkin ◽  
Rajan Gogna
Keyword(s):  
Cancer Progression ◽  
Hippo Pathway ◽  
Cancer Therapeutics ◽  
Protein Isoforms ◽  
Cell Junction ◽  
Cell Competition ◽  
Molecular Features ◽  
Oncogenic Pathways ◽  
Diagnostic Potential ◽  
The Impact

Cell competition (CC) is a feature that allows tumor cells to outcompete and eliminate adjacent cells that are deemed less fit. Studies of CC, first described in Drosophila melanogaster, reveal a diversity of underlying mechanisms. In this review, we will discuss three recent studies that expand our understanding of the molecular features governing CC. In particular, we will focus on a molecular fitness fingerprint, oncogenic pathways, and the importance of cell junction stability. A fitness fingerprint, mediated by flower (hFWE) protein isoforms, dictates that cells expressing the flower-win isoforms will outcompete adjacent flower-loss-expressing cells. The impact of the flower protein isoforms is seen in cancer progression and may have diagnostic potential. The yes-associated protein (YAP) and TAZ transcription factors, central mediators of the oncogenic Hippo pathway, elevate peritumoral fitness thereby protecting against tumor progression and provide a suppressive barrier. Similarly, COL17A1 is a key component in hemidesmosome stability, and its expression in epidermal stem cells contributes to fitness competition and aging characteristics. The contributions of these pathways to disease development and progression will help define how CC is hijacked to favor cancer growth. Understanding these features will also help frame the diagnostic and therapeutic possibilities that may place CC in the crosshairs of cancer therapeutics.

scholarly journals The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 535
Author(s):  
Anouk E. Hentschel ◽  
Rianne van den Helder ◽  
Nienke E. van Trommel ◽  
Annina P. van Splunter ◽  
Robert A. A. van Boerdonk ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bladder Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Bladder Tumor ◽  
Great Promise ◽  
Tumor Tissues ◽  
Catheter Urine ◽  
Tumor Dna ◽  
Urogenital Cancers

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

scholarly journals ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models

2020 ◽  
Vol 22 (1) ◽  
pp. 241
Author(s):  
Dong-Hoon Yeom ◽  
Yo-Seob Lee ◽  
Ilhwan Ryu ◽  
Sunju Lee ◽  
Byungje Sung ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Bispecific Antibody ◽  
Phase 1 ◽  
Tumor Vessel ◽  
Vegf Inhibitors ◽  
Xenograft Models ◽  
Antibody Targeting

Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.

scholarly journals Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Iman Akhlaghipour ◽  
Amir Reza Bina ◽  
Mohammad Reza Abbaszadegan ◽  
Meysam Moghbeli
Keyword(s):  
Risk Factors ◽  
Early Detection ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Early Detection Of Cancer ◽  
Iranian Population ◽  
Molecular Diagnostic ◽  
Genomic Changes ◽  
Incidence And Mortality ◽  
Transcriptional Alterations

AbstractCancer is one of the main health challenges and leading causes of deaths in the world. Various environmental and genetic risk factors are associated with tumorigenesis. Epigenetic deregulations are also important risk factors during tumor progression which are reversible transcriptional alterations without any genomic changes. Various mechanisms are involved in epigenetic regulations such as DNA methylation, chromatin modifications, and noncoding RNAs. Cancer incidence and mortality have a growing trend during last decades among Iranian population which are significantly related to the late diagnosis. Therefore, it is required to prepare efficient molecular diagnostic panels for the early detection of cancer in this population. Promoter hyper methylation is frequently observed as an inhibitory molecular mechanism in various genes associated with DNA repair, cell cycle regulation, and apoptosis during tumor progression. Since aberrant promoter methylations have critical roles in early stages of neoplastic transformations, in present review we have summarized all of the aberrant methylations which have been reported during tumor progression among Iranian cancer patients. Aberrant promoter methylations are targetable and prepare novel therapeutic options for the personalized medicine in cancer patients. This review paves the way to introduce a non-invasive methylation specific panel of diagnostic markers for the early detection of cancer among Iranians.

Erythroid-Stimulating Agents in Cancer Therapy: Potential Dangers and Biologic Mechanisms

2009 ◽  
Vol 27 (25) ◽  
pp. 4217-4226 ◽  
Author(s):  
Brandon K. Hadland ◽  
Gregory D. Longmore
Keyword(s):  
Quality Of Life ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Detrimental Effect ◽  
Randomized Clinical Trials ◽  
Supportive Therapy ◽  
Endogenous Erythropoietin ◽  
Per Se ◽  
Erythropoietin Stimulating Agents

Erythropoietin-stimulating agents (ESAs) were originally designed to replace endogenous erythropoietin in patients with anemia secondary to renal failure. Their use has subsequently been expanded to include patients with anemia of other causes, including cancer patients, in whom deficiency of erythropoietin, per se, is not the primary cause of anemia. Although early studies showed promise of ESA administration in reducing the need for transfusions and improving the quality of life in cancer patients, several large randomized clinical trials have recently shown a potential detrimental effect of ESA administration on tumor progression and survival in these patients. These studies have called into question the safety of ESAs as supportive therapy in patients being treated for oncologic conditions. However, numerous questions remain to be addressed regarding the design of these studies, the effect of various targeted hemoglobin levels, and the potential biologic mechanisms proposed to explain promotion of tumor progression and reduced survival.

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