Search

Concetta Cafiero,1,* Agnese Re,2,* Alessandra Micera,3,* Raffaele Palmirotta,4 Delio Monaco,5 Francesca Romano,6 Claudia Fabrizio,7 Raffaele Di Francia,8 Andrea Cacciamani,3 Pier Luigi Surico,9 Gerardo D’Amato,10 Salvatore Pisconti1 1Medical Oncology, SG Moscati Hospital, Taranto, Italy; 2CNR-IASI, Catholic University of Sacred Heart, Rome, Italy; 3Research Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, Rome, Italy; 4Department of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, Bari, Italy; 5Radiology, SG Moscati Hospital, Taranto, Italy; 6Department of Precision Medicine, Luigi Vanvitelli University of Campania, Napoli, Italy; 7Infectious Disease Unit, SG Moscati Hospital, Taranto, Italy; 8Italian Association of Pharmacogenomics and Molecular Diagnostics, Ancona, Italy; 9Oncology and Hematology Department, F Miulli Hospital, Acquaviva delle Fonti, Italy; 10Endocrine and Metabolic Surgery, A Gemelli Polyclinic Foundation, Rome, Italy*These authors contributed equally to this workCorrespondence: Alessandra MiceraResearch Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, 6 via di Santo Stefano Rotondo, Rome 00184, ItalyTel +39-06-4554-1191Email alessandra.micera@fondazionebietti.itRaffaele PalmirottaDepartment of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, ItalyEmail raffaelepalmirotta@gmail.comAbstract: The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.Keywords: Covid-19, SARS-CoV2, drug effects, pharmacogenomics, pharmacogenetics, in silico, ADR

The introduction of highly active antiretroviral therapy (ART) has deeply modified the outcome of HIV patients by improving their overall survival and ameliorating their quality of life (QoL). The prolongation of these patients’ survival has led to an increased risk of highly diffused non-infectious diseases, e.g., cardiovascular diseases, endocrine disease, neurological diseases, and cancer. The management of antiretroviral therapy and anticancer agents (AC) can be challenging, due to the possible drug-drug interactions (DDI) between AC and ART. For this reason, a multidisciplinary approach is always preferred as demonstrated by the GICAT (Italian Cooperation Group on AIDS and Tumors). This review aims to analyze the current scientific data regarding the possible effects of ART on the management of HIV-positive cancer patients and to evaluate the possible DDIs that must be taken into consideration when co-administrating ART and AC. A collaboration between all the involved professional figures, particularly infectious disease specialists and oncologists, represents the key to the correct managing of these patients in order to guarantee the best oncological outcome possible. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The curative hepatocellular carcinoma (HCC) therapy was traditionally based on surgical or loco-regional ablation approach. However, HCC is a solid tumor characterized by a highest level of vascularization; therefore, angiogenesis inhibitor could play a pivotal role in the pharmacological therapeutic approach. Despite the low number of approved drugs, a wide range of multi-kinase and MET inhibitor is currently being evaluated in phase II and III study. In this review, we described all the drugs that have shown efficacy in recently and ongoing trials. Moreover, the immunotherapy represents a recent challenge in the HCC treatment. The strategy based on the production of multi-epitope, multi-HLA peptide vaccine naturally processed and presented on primary tumor tissues of HCC patients. A further upgrade of cancer vaccine could be represented by the combination of metronomic chemotherapy and checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Current precision medicine approaches offer powerful tools to optimize medication regimens; however, the potential impact of these tools in cancer patients with multiple drug treatments has not fully appreciated yet. Here we describe a planning project scheduled to start in the next six months. PATIENTS AND METHODS: The overall endpoint of this project is to explore the potential association between the presence of individual genetic profile and severe toxicity rates in so-called "frail" cancer patients, using a nested case-control study design. The pilot study includes the detection of the individual pharmacogenetic profile of 150 (cases), prospect enrolled cancer "frail" patients, and 150 (control) retrospectively paired enrolled individuals. Methods for addressing the primary endpoint include: (a) Evaluation of cost-effectiveness analysis by recording QALY criteria; (b) Data recording by a brief self-administered questionnaire used to evaluate the adherence of a patient's tests and the impact of this genotyping on the patient's adverse drug reactions (ADR); (c) A sample size of paired (for age, gender, education, social status, geriatric syndromes, number of medications and comorbidities) 150 (cases) and 150 (controls); (d) Genotyping method choice by current widely diffuse platforms. RESULTS: The investigators believe that genotype screening and the management of the overall cost of health care personalized therapy has the potential to reduce the health care costs of the Italian national health system (SSN). CONCLUSIONS: Finally, the innovative issue of this project is to advocate the creation of a new model of the co-operative team (Physicians, pharmacist, geneticist and lab manager) that join for planning the most appropriated personalized therapy for their patient. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Hair loss generates severe psychosocial implications. To date, exploring the prognostic factors of possible clinical benefit of autologous blood concentrate platelet rich plasma (PRP) was failed. The aim of our pilot study was to explore the correlation between the individual inflammation genetic profile and PRP efficacy in the treatment of hair follicle regeneration. PATIENTS AND METHODS: 41 volunteers (25 men, 16 women) took part in this retrospective study. All the patients were scheduled for 4 sessions of PRP application with intervals of 40-60 days. All the patients were checked up at 6 weekly intervals for 6 months and, then, at the end of the first year. A panel of 5 polymorphisms on 4 genes (IL-1a, IL-1b, IL-6, and IL-10) implicated in the individual genetic inflammation profile were performed. RESULTS: A significant increase rate in hair density was noticed after the third month of treatment in 32/41 (78%) of the subjects. We found an interesting association between the pro-inflammatory cytokine IL-1a polymorphism C>A (rs17561) and responders to PRP treatment. The cases carrying C/C genotype (coding for Ser114) were 21 (66%) in responders and only 2 (22%) in non-responders (p<0.05). In addition, about IL-1a, the frequency of G/G genotype in responder patients was over two times lower in responder (31%) than in non-responder patients (78%). CONCLUSIONS: Our pilot study demonstrated a correlation between the individual genetic inflammatory profile and the efficacy of the PRP treatment in males. On the contrary, in females, it showed a negative correlation. IL-1a could be used as a prognostic value for PRP efficacy. Also, these results provide preliminary evidence that may encourage the design of controlled clinical trials to properly test this modus operandi on a large number of subjects. [ABSTRACT FROM AUTHOR]

It is well-known that 75% of risk factors of chronic liver disease (CLD) are related to nutrition. These circumstances potentially progress towards liver steatosis, fibrosis and hepatocellular carcinoma (HCC). It still represents an enormous problem for the economy of public health worldwide. Furthermore, validated prevention programs could be the solution. Recent knowledge in understanding molecular determinants of energy liver metabolism and new genetic markers offers new insights into the pathogenesis of CLD and HCC. The main rationale of the present issue is to provide a summary of recent insights into the inherited variants regulating lipid metabolism (steatohepatitis) and acquired mutation for early diagnosis of HCC, specifically focusing on the significance of antioxidant agents and genotyping tests as a cost-effectiveness tool for the prevention of liver disease. Several national healthy programs worldwide promote the daily use of antioxidant nutrients either for the prevention and/or as complementary and alternative medicines (CAM). This review could be advising for the planning of a large-scale clinical trial including a combination strategy of antioxidant agents and genotyping tests in patients with high risk of CLD. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the third leading cause of cancer death in both sexes worldwide, with the highest estimated mortality rates in Eastern Asia and the lowest in Northern America. However, the availability of modern treatment has improved the survival and the prognosis is often poor due to biological characteristics of the disease. In oncology, we are living in the “Era” of target treatment and, to know biological aspects, prognostic factors and predictive response informations to therapy in GC is mandatory to apply the best strategy of treatment. The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma (NHL) featured by participation of the lymph nodes, spleen, blood and bone marrow with a short remission period to standard therapies and a median overall survival of 4-5 years. PATIENTS AND METHODS: In this study, we compare the levels of bcl-1/JH fusion products detected by q-PCR in the concurrent peripheral blood (PB) and bone marrow (BM) aspirate samples from 7 patients with MCL. RESULTS: In patients with moderate to high levels of bcl-1/JH copies, the results of q-PCR analysis of PB and BM aspirate samples correlate well. In patients with high levels of bcl-1/JH copies, instead, PB levels are a good indication of tumor burden. Finally, in patients with low levels of bcl-1/JH copies, the t(11;14) may be detected by identification of neoplastic cells. CONCLUSIONS: Our data suggest that PB can be reliably used in place of BM aspirate both for detection of translocation status during minimal residual disease monitoring and for a possible molecular relapse, especially in those patients who have moderate to high levels of bcl-1/JH copies. If these results will be confirmed on a wider number of MCL patients, future study will be required to address the issue. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy. [ABSTRACT FROM AUTHOR]

The advent of antiretroviral therapy (ART) has markedly extended the survival rates of patients with human immunodeficiency virus (HIV), leading to suppression even though not eradication of HIV. In HIV infected patients, cancer has become a growing problem, representing the first cause of death. A large number of worldwide studies have shown that HIV infection raises the risk of many non-AIDS defining cancers (NADCs), including squamous cell carcinoma of the anus (SCCA), testis cancer, lung cancer, cancer of the colon and rectum (CRC), skin (basal cell skin carcinoma and melanoma), Hodgkin disease (HD) and hepato-cellular carcinoma (HCC). Generally in HIV positive patients NADCs are more aggressive and in advanced stage disease than in the general population. In the ART era, however, the outcome of HIV positive patients is more similar as in the general population. Only about lung cancer the outcome seems different between HIV positive and HIV negative patients. The aim of this article is to provide an update on NADCs within the activity of the Italian Cooperative Group on AIDS and Tumors (GICAT) to identify clinical prognostic and predicting factors in patients with HIV infection included in the GICAT. [ABSTRACT FROM AUTHOR]

Recently, several methods to assess the quality of cost-effectiveness, cost-utility and cost-benefit in the pharmacogenomic field have become available. A relevant example is the National Institute for Health and Clinical Excellence (NICE). NICE forms a diverse clinical Advisory committee, which stimulates Pharma and Academic communities to produce a robust set of data, including the design and data source, for economic models of personalized healthcare. Personalized medicine includes genomic tests of each patients and their disease into their clinical treatments, so as minimize toxicity and maximize benefits. It is well known that Pharmacogenomics (PG) tests, performed before drug treatment, lower overall medical costs and provide higher quality of life and longer life expectancy. In this issue relative costs of genotyping methods and platforms, were evaluated by "manually cured criteria" due to lack of specific guidelines. Finally, with the progress made in this scenario over the next five years, health decision-making may able to accelerating the translation of genetic technologies into routine clinical laboratory. [ABSTRACT FROM AUTHOR]

AIM: Both Fluoropirimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat lung, colorectal, ovarian, breast, head/neck, and genitourinary cancers. However, the efficacy of FluOx-based therapy is often compromised because of the severe risk of toxicity. Stratification of patients for multidrug response is a promising strategy for cancer treatment and personalized therapy. METHODS: Here, we review the late findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. Several criteria were used to select a genotyping panel tests, including dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), Glutathione S-transferase (GSTP1), and ATP-binding cassette, subfamily C member 2 (ABCC2). RESULTS: Results of allelic status from 7 validated polymorphism assays, allow the stratification of the patients who are most likely to respond to FluOx treatments. Also, we will take in consideration the usefulness and costs of the methods used to detect these polymorphisms. CONCLUSIONS:With these pharmacogenomics markers, the oncologists will have new means based on the genetic profile of the individual, to make treatment decisions for their patients in order to maximize benefits and minimize toxicity. [ABSTRACT FROM AUTHOR]

Background: Promise in the future, a disease could be ranked into genetic categories, allowing bespoke tailoring of medicine to maximize therapeutic effects and to reduce the potential for adverse drug response. This new feature requires for health professionals to have competencies not only for the basic skills of their discipline, but also for the understanding on why, when, and how that knowledge should be applied to improve personalized therapies for their patients. Current opinion on basic competences of health professions includes knowledge and skills on two fundamental features: (1) genetics of disease, to allow the understanding and the identification of diseases associated to genetic variations, and to facilitate the development of new genomic tests; and (2) ethical, social and economical implications that are fundamental to identify those factors that might contribute to a successful integration of pharmacogenomics into international health and public policy. Aim: Briefly, we described (1) current knowledge on genetic variations that interact with therapies and the need to detect them; (2) the most common available methods for detecting mutations; and (3) ethical, social and economic issues related to pharmacogenetic testing and recording of genetic information (e.g., critical evaluation of the development of new tests, privacy, the current absence of public reimbursement, etc). Conclusions: These could be useful recommendations for academic institutions and educational programs to prepare health professionals with the necessary abilities for their future practice. [ABSTRACT FROM AUTHOR]

Background: Many clinicians acknowledge the importance of genetics in drug response and are favourable about using genetic tests to guide therapy. The 5-Fluorouracil (5-FU) is the backbone of different regimens for the treatment of several solid tumours. Unlikely, some patients develop gastrointestinal and hematologic toxicities when treated by the 5-FU, leading to the suspension of therapy. Current evidences of pharmacogenomics, have reported different polymorphisms associated to genes involved with fluoropyrimidine biotransformation. A multitude of methods has been applied to assess the mutational status of these genes, without defining a golden standard for the daily diagnostic routine, so far. Aims: Some adverse drug response due to the administration of 5-FU can be predicted through pharmacogenomics testing tools. This report reviews the recent findings on the polymorphism for genes that are involved in the biotransformation of the drug and its association with the toxic effect in patients receiving 5-FU in mono o polychemoterapy. Most common fluoropyrimidines-based regimens are finely described. Also, we will take in considerations the recent methods used to identify these genetic alterations. Conclusion: Recent and evolving technological advances for genotyping will result in personalized treatment. In the next future the oncologists will have new means based on the genetic composition of the individual, to make treatment decisions for their patients maximizing benefit and minimizing toxicity. Based on these purpose, clinician and lab manager may join together to evaluate advantages and limitation, in terms of costs and applicability, of the most appropriate methods to set molecular diagnostics of 5-FU pharmacogenomics tests. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article regarding the identification of one of the signals involved in hepatocellular carcinoma (HCC) sensitivity cells to cisplatin in c-Jun N-terminal kinase (JNK) signaling pathway.

The article focuses on current predictive pathology in the clinical setting of colorectal cancer. It mentions that two genes belong to MAPK pathway, RAS and B-RAF, HER2 is a transmembrane receptor implied in PI3K pathway, and microsatellites are four proteins which forming two heterodimers are designate to correct DNA errors.

A letter to the editor is presented in response to the article "The Expression of PD-L1 APE1 and P53 in Hepatocellular Carcinoma and Its Relationship to Clinical Pathology" by Kan and Dong that was published in a 2015 issue.