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Background: Genome-wide association studies (GWAS) are important for the acceleration of crop improvement through knowledge of marker-trait association (MTA). This report used DArT SNP markers to successfully perform GWAS on agro-morphological traits using 270 bambara groundnut [Vigna subterranea (L.) Verdc.] landraces sourced from diverse origins. The study aimed to identify marker traits association for nine agronomic traits using GWAS and their candidate genes. The experiment was conducted at two different locations laid out in alpha lattice design. The cowpea [Vigna unguiculata (L.) Walp.] reference genome (i.e. legume genome most closely related to bambara groundnut) assisted in the identification of candidate genes., Results: The analyses showed that linkage disequilibrium was found to decay rapidly with an average genetic distance of 148 kb. The broadsense heritability was relatively high and ranged from 48.39% (terminal leaf length) to 79.39% (number of pods per plant). The GWAS identified a total of 27 significant marker-trait associations (MTAs) for the nine studied traits explaining 5.27% to 24.86% of phenotypic variations. Among studied traits, the highest number of MTAs was obtained from seed coat colour (6) followed by days to flowering (5), while the least is days to maturity (1), explaining 5.76% to 11.03%, 14.5% to 19.49%, and 11.66% phenotypic variations, respectively. Also, a total of 17 candidate genes were identified, varying in number for different traits; seed coat colour (6), days to flowering (3), terminal leaf length (2), terminal leaf width (2), number of seed per pod (2), pod width (1) and days to maturity (1)., Conclusion: These results revealed the prospect of GWAS in identification of SNP variations associated with agronomic traits in bambara groundnut. Also, its present new opportunity to explore GWAS and marker assisted strategies in breeding of bambara groundnut for acceleration of the crop improvement., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Understanding the genetic structure and diversity of crops facilitates progress in plant breeding. A collection of 270 bambara groundnut (Vigna subterrenea L) landraces sourced from different geographical regions (Nigeria/Cameroon, West, Central, Southern and East Africa) and unknown origin (sourced from United Kingdom) was used to assess genetic diversity, relationship and population structure using DArT SNP markers. The major allele frequency ranged from 0.57 for unknown origin to 0.91 for West Africa region. The total gene diversity (0.482) and Shannon diversity index (0.787) was higher in West African accessions. The genetic distance between pairs of regions varied from 0.002 to 0.028 with higher similarity between Nigeria/Cameroon-West Africa accessions and East-Southern Africa accessions. The analysis of molecular variance (AMOVA) revealed 89% of genetic variation within population, 8% among regions and 3% among population. The genetic relatedness among the collections was evaluated using neighbor joining tree analysis, which grouped all the geographic regions into three major clusters. Three major subgroups of bambara groundnut were identified using the ADMIXTURE model program and confirmed by discriminant analysis of principal components (DAPC). These subgroups were West Africa, Nigeria/Cameroon and unknown origin that gave rise to sub-population one, and Central Africa was sub-population two, while Southern and East Africa were sub-population three. In general, the results of all the different analytical methods used in this study confirmed the existence of high level of diversity among the germplasm used in this study that might be utilized for future genetic improvement of bambara groundnut. The finding also provides new insight on the population structure of African bambara groundnut germplasm which will help in conservation strategy and management of the crop., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Despite the wide adoption of tumor molecular profiling, there is a dearth of evidence linking molecular biomarkers for treatment selection to prediction of treatment outcomes in patients with metastatic pancreatic cancer. We initiated a pilot study to test the feasibility of designing a larger phase II trial of molecularly tailored treatment for metastatic pancreatic cancer. Methods: Our study aimed to assess the feasibility of following a treatment algorithm based on the expression of three published predictive markers of response to chemotherapy: ribonucleotide reductase catalytic subunit M1 (for gemcitabine); excision repair cross-complementation group 1 (for platinum agents); and thymidylate synthase (for 5-fluorouracil) in patients with untreated, metastatic pancreatic cancer. Results of the tumor biopsy analysis were used to assign patients to one of seven doublet regimens. Key secondary objectives included response rate (RR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2012 and March 2015, 30 patients were enrolled into the study. Ten patients failed screening primarily due to inadequate tumor tissue availability. Of the remaining 20 patients, 19 were assigned into 6 different chemotherapy doublets, and achieved an RR of 28%, with a DCR rate of 78%. The median PFS and OS were 5.78 and 8.21 months, respectively. Conclusions: The incorporation of biomarkers into a treatment algorithm is feasible and resulted in a PFS and OS similar to other doublet therapies for patients with metastatic pancreatic cancer. Based on the results from this pilot study, a larger phase II randomized trial of molecularly targeted therapy versus physicians' choice of standard of care has been initiated in the second-line setting (NCT02967770)., Competing Interests: No competing financial interests exist.

Objectives: Adenocarcinoma of the pancreas represents the third leading cause of cancer-related death in the United States. Drug combinations, FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel, showed a clinically meaningful benefit when compared with single-agent gemcitabine in phase III trials. The goal of this study was to investigate whether there was an increase in overall survival (OS) for patients treated for metastatic pancreatic cancer after the introduction of the above regimens., Materials and Methods: Patients were grouped into 2 treatment eras that were before and after the introduction of these newer chemotherapeutic regimens; 2006-2010 and 2011-2015, respectively. Baseline demographics and disease-related variables were collected from metastatic pancreatic cancer treated at the Barbara Ann Karmanos Cancer Institute in Detroit, MI., Results: When stratified by treatment era, the later era had an improvement in survival (hazard ratio for death of 0.61; P=0.005). Median OS was 8.97 and 9.95 months for the earlier (n=59) versus latter era (n=99), respectively. There was an increase from 28.3% to 38.9% at 12 months between the earlier and later era, an improvement of 37.4%. African Americans had a worse outcome with a hazard ratio of 1.63 (P=0.02) for death. When comparing the eras, Caucasians had a longer median OS in each era in addition to having a greater improvement in median OS between eras., Conclusions: There was a modest improvement in median OS between 2006-2010 and 2011-2015 with the introduction of newer chemotherapeutic regimens. However, there has been no significant improvement in outcomes for African Americans or in short-term survival.

Pancreatic ductal adenocarcinoma (PDAC) remains a challenging disease that is mostly diagnosed late in the course of the illness. Unlike other cancers in which measurable successes have been achieved with traditional chemotherapy, targeted therapy, and, recently, immunotherapy, PDAC has proved to be poorly responsive to these treatments, with only marginal to modest incremental benefits using conventional cytotoxic therapy. There is, therefore, a great unmet need to develop better therapies based on improved understanding of biology and identification of predictive and prognostic biomarkers that would guide therapy. miRNAs are small noncoding RNAs that regulate the expression of some key genes by targeting their 3'-untranslated mRNA region. Aberrant expression of miRNAs has been linked to the development of various malignancies, including PDAC. A series of miRNAs have been identified as potential tools for early diagnosis, prediction of treatment response, and prognosis of patients with PDAC. In this review, we present a summary of the miRNAs that have been studied in PDAC in the context of disease biology., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related mortality in the United States. Surgical resection of early and localized disease provides the only chance for a cure; however, the majority of patients who have PDAC present with advanced disease that cannot be removed surgically. In the minority of patients who undergo surgical resection, there is a high rate of disease recurrence that eventually leads to death. The use of systemic therapy improves the outcome of patients who undergo surgery by targeting early micrometastatic disease. This review focuses on the medical management (both chemotherapy and radiation therapy) of surgically resectable pancreatic cancer, including the findings of recent practice-changing clinical trials that favor combination chemotherapy for adjuvant treatment and neoadjuvant chemoradiation therapy. The review also highlights important ongoing trials that aim to improve outcomes in patients with resectable pancreatic cancer.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer related mortality in the United States in 2030, with a 5-year overall survival of less than 10% despite decades of extensive research. Pancreatic cancer is marked by the accumulation of complex molecular changes, complex tumor-stroma interaction, and an immunosuppressive tumor microenvironment. PDAC has proven to be resistant to many cytotoxic, targeted and immunologic treatment approaches. Areas covered: In this paper, we review the major areas of research in PDAC, with highlights on the challenges and areas of opportunity for personalized treatment approaches. Expert commentary: The focus of research in pancreatic cancer has moved away from developing conventional cytotoxic combinations. The marked advances in understanding the molecular biology of this disease especially in the areas of the microenvironment, metabolism, and DNA repair have opened new opportunities for developing novel treatment strategies. Improved understanding of molecular abnormalities allows the development of personalized treatment approaches.

Purpose: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC)., Methods: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03., Results: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months., Conclusion: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS., Gov Identifier: NCT01205828.