Oncology Reviews 2020-02-16T18:09:25+00:00 Paola Granata Open Journal Systems <p><strong>Oncology Reviews</strong> is an Open Access, peer-reviewed, international journal that publishes authoritative state-of-the-art reviews on preclinical and clinical aspects of oncology.</p> <p>The journal provide up-to-date information on the latest achievements in different fields of oncology for both practising clinicians and basic researchers. <strong>Oncology Reviews</strong> aims at being international in scope and readership, as reflected also by its Editorial Board, gathering the world leading experts in both pre-clinical research and everyday clinical practice.</p> <p>The journal is open for publication of supplements, monothematic issues and for publishing abstracts of scientific meetings; conditions can be obtained from the Editor-in-Chief or the publisher.</p> <p>The journal was previously published by Springer Italy; since 2012 <strong>Oncology Reviews</strong> passed on to PAGEPress.&nbsp;</p> MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis 2020-02-16T18:09:25+00:00 Arslaan Javaeed Sanniya Khan Ghauri <p>The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated <em>via</em> monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high <em>versus</em> low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P&lt;0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P&lt;0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.</p> 2019-07-22T10:30:36+00:00 ##submission.copyrightStatement## Prognostic significance of mutated genes in megakaryocytic disorders 2020-02-16T18:09:25+00:00 Ali Amin Asnafi Mohammad bagher Mohammadi Hadi Rezaeeyan Nader Davari Najmaldin Saki <p>Megakaryopoiesis is a process during which platelets that play a major role in hemostasis are produced due to differentiation and maturation of megakaryocytic precursors. Several genes, including oncogenes and tumor suppressor genes, play a role in the regulation of this process. This study was conducted to investigate the oncogenes and tumor suppressor genes as well as their mutations during the megakaryopoiesis process, which can lead to megakaryocytic disorders. Relevant literature was identified by a PubMed search (1998-2019) of English language papers using the terms ‘<em>Megakaryopoiesis’, ‘Mutation’, ‘oncogenes’, </em>and<em> ‘Tumor Suppressor’.</em> According to investigations, several mutations occur in the genes implicated in megakaryopoiesis, which abnormally induce or inhibit megakaryocyte production, differentiation, and maturation, leading to platelet disorders. GATA-1 is one of the important genes in megakaryopoiesis and its mutations can be considered among the factors involved in the incidence of these disorders. Considering the essential role of these genes (such as GATA- 1) in megakaryopoiesis and the involvement of their mutations in platelet disorders, study and examination of these changes can be a positive step in the diagnosis and prognosis of these diseases.</p> 2019-07-22T10:53:24+00:00 ##submission.copyrightStatement## Epigenetic modification in the expression of p73 p73 - epigenetic target for anticancer therapy 2020-02-16T18:09:24+00:00 Faiza Naseer Mohammad Saleem <p>A p73 is a new member of p53 family of transcription factor, having two types. First is TAp73, transcriptionally active and expressed <em>via</em> upstream promoter as a tumor suppressor and vital apoptotic inductor, it also has a key role in cell cycle arrest/differentiation and Second is ΔNp73 that is transcriptionally inactive and expressed via downstream regulator as oncogenes. Both types are expressed in various isoforms, which originate from alternative splicing events at the C-terminus. Upon DNA damage, posttranslational modifications cause conformational changes in various amino acid residues via induction or inhibition of various proteins, which are present in the structural domains of p73. These modifications may cause up- or down-regulation of p73 expression levels, as well as alters the transcriptional activity and/or stability of the protein. In this review, we have made an effort to assemble all existing data regarding the role of p73, its modification and after effects in cancer.</p> 2019-07-24T13:07:57+00:00 ##submission.copyrightStatement## Current promising treatment strategy for glioblastoma multiform: A review 2020-02-16T18:09:22+00:00 Sanjib Bahadur Arvind Kumar Sahu Pragya Baghel Suman Saha <p>Glioblastoma multiform (GBM) is a heterogeneous group of primary neoplasm resistant to conventional therapies. Due to their infiltrative nature it not fully isolated by aggressive surgery, radiation and chemotherapy showing poor prognosis in glioma patients. Unfortunately, diagnosed patients die within 1.5-2 year treatment schedule. Currently temozolomide (TMZ) is the first choice for the prognosis of GBM patients. TMZ metabolites methyl triazen imidazol carboxamide form complex with alkyl guanine alkyl transferase (O6 MGMT- DNA repair protein) induced DNA damage following resistance properties of TMZ and inhibit the overall survival of the patients. Last few decades different TMZ conjugated strategy is developed to overcome the resistance and enhance the chemotherapy efficacy. The main aim of this review is to introduce the new promising pharmaceutical candidates that significantly influence the therapeutic response of the TMZ in context of targeted therapy of glioblastoma patients. It is hoped that this proposed strategy are highly effective to overcome the current resistance limitations of TMZ in GBM patients and enhance the survival rate of the patients.</p> 2019-07-25T09:45:47+00:00 ##submission.copyrightStatement## CDK4/6 inhibitors in advanced breast cancer, what is beyond? 2020-02-16T18:09:22+00:00 Amrallah A. Mohammed Hanaa Rashied Fifi Mostafa Elsayed <p>Resistant to hormonal treatment considered the main clinical challenge in the management of advanced breast cancer (ABC). The use of CDK4/6 inhibitors (CDK4/6I) may change the treatment landscape. In this mandated review, we will focus on the applicable role of CDK4/6I in the management of HR+/HER2- ABC, mechanisms of resistance, and promising future implementation.</p> 2019-07-29T09:19:16+00:00 ##submission.copyrightStatement## Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy 2020-02-16T18:09:21+00:00 Jacob S. Bowers Stefanie R. Bailey Mark P. Rubinstein Chrystal M. Paulos E. Ramsay Camp <p>Pancreatic adenocarcinoma (PDAC) remains a formidable disease that needs improved therapeutic strategies. Even though immunotherapy has revolutionized treatment for various solid tumor types, it remains largely ineffective in treating individuals with PDAC. This review describes how the application of genome-wide analysis is revitalizing the field of PDAC immunotherapy. Major themes include new insights into the body’s immune response to the cancer, and key immunosuppressive elements that blunt that antitumor immunity. In particular, new evidence indicates that T cell-based antitumor immunity against PDAC is more common, and more easily generated, than previously thought. However, equally common are an array of cellular and molecular defenses employed by the tumor against those T cells. These discoveries have changed how current immunotherapies are deployed and have directed development of novel strategies to better treat this disease. Thus, the impact of genomic analysis has been two-fold: both in demonstrating the heterogeneity of immune targets and defenses in this disease, as well as providing a powerful tool for designing and identifying personalized therapies that exploit each tumor’s unique phenotype. Such personalized treatment combinations may be the key to developing successful immunotherapies for pancreatic adenocarcinoma.</p> 2019-08-01T09:18:55+00:00 ##submission.copyrightStatement## Recent trends in predictive biomarkers for determining malignant potential of oral potentially malignant disorders 2020-02-16T18:09:21+00:00 Gargi S. Sarode Sachin C. Sarode Nikunj Maniyar Nilesh Sharma Sujata Yerwadekar Shankargouda Patil <p>Despite of the tremendous advancements in the field of cancer prevention, detection and treatment, the overall prognosis of oral squamous cell carcinoma (OSCC) still remains poor. This can be partly imparted to the lack of early detection of oral potentially malignant disorders (OPMDs), especially those at a higher risk of progression into OSCC. Over years, various specific and non-specific markers have been introduced that could predict the malignant transformation of OPMDs; however detail information on these OPMD markers in a concise manner is lacking. Moreover, their use on daily clinical basis still remains questionable. With continuous research in the field of cytology and genomics, several contemporary biomarkers have been discovered that are not yet foregrounded and proved to be more promising than those used conventionally. Here, in the present paper, we overview several recently concluded predictive biomarkers with special emphasis on their role in molecular pathogenesis of OSCC transformation. These markers can be used for risk assessment of malignant transformation in patients with OPMDs as well as for prophylactic conciliation and fair management of the high-risk OPMD patient group.</p> 2019-09-10T10:13:35+00:00 ##submission.copyrightStatement## Omics-based insights into therapy failure of pediatric B-lineage acute lymphoblastic leukemia 2020-02-16T18:09:20+00:00 Suliman A. Alsagaby <p>B-lineage acute lymphoblastic leukemia (B-ALL) is the most common type of cancer seen in children and is characterized by a variable clinical course. Although there have been remarkable improvements in the therapy outcomes of pediatric B-ALL, treatment failure remains the leading-cause of death in 18% of the afflicted patients during the first 5 years after diagnosis. Molecular heterogeneities of pediatric B-ALL play important roles as determinants of the therapy response. Therefore, many of these molecular abnormalities have an established prognostic value in the disease. The present review discusses the omics-based revelations from epigenomics, genomics, transcriptomics and proteomics about treatment failure in pediatric B-ALL. Next it highlights the promise of the molecular aberration-targeted therapy to improve the treatment outcomes.</p> 2019-09-10T10:25:47+00:00 ##submission.copyrightStatement## Therapeutic options for ampullary carcinomas. A review 2020-02-16T18:09:20+00:00 Dileep Kumar Reddy Regalla Rojymon Jacob Ashish Manne Ravi Kumar Paluri <p>Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.</p> 2019-09-10T10:34:07+00:00 ##submission.copyrightStatement## Potential effect of probiotics in the treatment of breast cancer 2020-02-16T18:09:19+00:00 Luis Mendoza <p>Breast cancer is one of the most important causes of cancerrelated morbidity and mortality in the world. Probiotics, as functional food, have the potential to act against breast cancer, as evidenced by cell-based and animal model experiments. Probiotic may be useful in prevention or treatment of breast cancer by modulating the gastrointestinal bacteria and the systemic immune system. However, large-scale clinical trials and intensive research are mandatory to confirm the <em>in vitro </em>and<em> in vivo</em> results and exploring the probiotics-related metabolic, immune, and molecular mechanisms in breast cancer. This current review summarizes the available data related to probiotics and their potential role in the treatment of breast cancer.</p> 2019-09-27T16:17:02+00:00 ##submission.copyrightStatement## Efficacy and safety profiles of programmed cell death-1/programmed cell death ligand-1 inhibitors in the treatment of triple-negative breast cancer: A comprehensive systematic review 2020-02-16T18:09:18+00:00 Gilbert Lazarus Jessica Audrey Anthony William Brian Iskandar <p>Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) showed great potentials in treating malignancies and may serve as potential therapies for TNBC. This systematic review aims to evaluate the efficacy and safety profiles of PD-1/PD-L1 inhibitors in the treatment of TNBC. Literature search was performed via PubMed, EBSCOhost, Scopus, and CENTRAL databases, selecting studies which evaluated the use of anti-PD-1/PDL1 for TNBC from inception until February 2019. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). Overall, 7 studies evaluating outcomes of 1395 patients with TNBC were included in this systematic review. Anti-PD-1/PD-L1 showed significant antitumor effect, proven by their promising response (objective response rate (ORR), 18.5-39.4%) and survival rates (median overall survival (OS), 9.2-21.3 months). Moreover, anti- PD-1/PD-L1 yielded better outcomes when given as first-line therapy, and overexpression of PD-L1 in tumors showed better therapeutic effects. On the other hands, safety profiles were similar across agents and generally acceptable, with grade ≥3 treatment- related adverse effects (AEs) ranging from 9.5% to 15.6% and no new AEs were experienced by TNBC patients. Most grade ≥3 AEs are immune-mediated, which are manifested as neutropenia, fatigue, peripheral neuropathy, and anemia. PD-1/PD-L1 inhibitors showed promising efficacy and tolerable AEs, and thus may benefit TNBC patients. Further studies of randomized controlled trials with larger populations are needed to better confirm the potential of these agents.</p> 2019-10-10T00:00:00+00:00 ##submission.copyrightStatement## Renal toxicity with mammalian target of rapamycin inhibitors: A meta-analysis of randomized clinical trials 2020-02-16T18:09:18+00:00 Ravi K. Paluri Guru Sonpavde Charity Morgan Jacob Rojymon Anastasia Hartzes Mar Radhika Gangaraju <p>A meta-analysis of randomized clinical trials (RCT) was done to determine the relative risk (RR) of acute kidney injury (AKI) with the use of mammalian target of rapamycin (mTOR) inhibitors. Citations from PubMed/Medline, clinical, package inserts and abstracts from major conferences were reviewed to include RCTs comparing arms with or without mTOR inhibitors. The RR of all grade AKI in patients taking mTOR inhibitors compared to patients not on mTOR inhibitors was 1.55 (95% CI: 1.11 to 2.16, P=0.010). There was no significant difference in the risk of high-grade AKI for the two groups (RR=1.29, P=0.118, 95% CI: 0.94 to 1.77). There was no significant difference in the incidence rates for either all grade or high-grade AKI between the two groups. There was no publication bias and the trials were of high quality per Jadad scoring.</p> 2019-11-25T17:07:15+00:00 ##submission.copyrightStatement## Evolving management of positive regional lymph nodes in melanoma: Past, present and future directions 2020-02-16T18:09:17+00:00 Rachel A. Fayne Francisco I. Macedo Steven E. Rodgers Mecker G. Möller <p>Sentinel lymph node (SLN) biopsy has become the standard of care for lymph node staging in melanoma and the most important predictor of survival in clinically node-negative disease. Previous guidelines recommend completion lymph node dissection (CLND) in cases of positive SLN; however, the lymph nodes recovered during CLND are only positive in a minority of these cases. Recent evidence suggests that conservative management (<em>i.e</em>. observation) has similar outcomes compared to CLND. We sought to review the most current literature regarding the management of SLN in metastatic melanoma and to discuss potential future directions.</p> 2019-11-28T14:01:35+00:00 ##submission.copyrightStatement##