scholarly journals Case Report: A Pancreatic Ductal Adenocarcinoma Patient With Concurrent Targetable Somatic Novel KANK1-ALK, UPP2-NTRK3 Fusion, and Pathogenetic Germline BRCA Mutation

2021 ◽  
Vol 11 ◽  
Author(s):  
Fan Meng ◽  
Le Lu ◽  
Yuan Tan ◽  
Qianqian Duan ◽  
Hongwei Lu
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Brca Mutation ◽  
Treatment Options ◽  
Survival Rates ◽  
Current Treatment ◽  
Ductal Adenocarcinoma ◽  
Genomic Alteration ◽  
Molecular Characteristics ◽  
Systematic Screening ◽  
Germline Brca Mutation

Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates. The current treatment options for PDAC are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of PDAC. Based on next-generation sequencing (NGS), we firstly presented a case about a KRAS wild-type pancreatic ductal adenocarcinoma patient harboring a concurrent targetable rare somatic novel KANK1-ALK, UPP2-NTRK3 fusion, and pathogenetic germline BRCA mutation. These two novel fusion statuses were assayed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Our findings demonstrated that comprehensive and systematic screening of PDAC for actionable genomic alteration may substantially improve the therapeutic prospects for a sizeable fraction of patients with PDAC. To improve the management of PDAC in an era of precision medicine, it is important to identify ALK or NTRK fusion-positive and pathogenic germline mutation subsets of patients who can benefit from targeted therapies.

scholarly journals Up-to-Date Tailored Systemic Treatment in Pancreatic Ductal Adenocarcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Caroline Y. K. Fong ◽  
Emma Burke ◽  
David Cunningham ◽  
Naureen Starling
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Tumour Microenvironment ◽  
Current Treatment ◽  
Ductal Adenocarcinoma ◽  
Molecular Features ◽  
Future Clinical Practice ◽  
To Come ◽  
Potential Methods

Despite intensive research efforts, pancreatic ductal adenocarcinoma is still regarded as an aggressive and life-limiting malignancy. Combination chemotherapy regimens that underpin the current treatment approach in the advanced setting have led to incremental survival gains in recent years but have failed to confer patients with a median overall survival that exceeds 12 months from diagnosis. Research has since focussed on understanding the role and interplay between various components of the desmoplastic stroma and tumour microenvironment, in addition to developing targeted therapies based on molecular features to improve the prognosis associated with this malignancy. This review will summarise the available systemic treatment options and discuss potential methods to refine the resolution of patient selection to enhance responses to currently available therapies. Furthermore, it will explore newer approaches anticipated to come to the fore of future clinical practice, such as agents targeting the DNA damage response and tumour microenvironment as well as immunotherapy-based combinations.

scholarly journals Radioimmunotherapy of Pancreatic Ductal Adenocarcinoma: A Review of the Current Status of Literature

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 481
Author(s):  
Ashleigh Hull ◽  
Yanrui Li ◽  
Dylan Bartholomeusz ◽  
William Hsieh ◽  
Barry Allen ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Synergistic Effects ◽  
Treatment Options ◽  
Survival Rates ◽  
Current Status ◽  
Ductal Adenocarcinoma ◽  
Physiological Factors ◽  
Tumour Control ◽  
Treatment Regimens ◽  
Clinical Trial Evidence

Pancreatic ductal adenocarcinoma (PDAC) has long been associated with low survival rates. A lack of accurate diagnostic tests and limited treatment options contribute to the poor prognosis of PDAC. Radioimmunotherapy using α- or β-emitting radionuclides has been identified as a potential treatment for PDAC. By harnessing the cytotoxicity of α or β particles, radioimmunotherapy may overcome the anatomic and physiological factors which traditionally make PDAC resistant to most conventional treatments. Appropriate selection of target receptors and the development of selective and cytotoxic radioimmunoconjugates are needed to achieve the desired results of radioimmunotherapy. The aim of this review is to examine the growing preclinical and clinical trial evidence regarding the application of α and β radioimmunotherapy for the treatment of PDAC. A systematic search of MEDLINE® and Scopus databases was performed to identify 34 relevant studies conducted on α or β radioimmunotherapy of PDAC. Preclinical results demonstrated α and β radioimmunotherapy provided effective tumour control. Clinical studies were limited to investigating β radioimmunotherapy only. Phase I and II trials observed disease control rates of 11.2%–57.9%, with synergistic effects noted for combination therapies. Further developments and optimisation of treatment regimens are needed to improve the clinical relevance of α and β radioimmunotherapy in PDAC.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

scholarly journals Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Beate Gündel ◽  
Xinyuan Liu ◽  
Matthias Löhr ◽  
Rainer Heuchel
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Ex Vivo ◽  
Treatment Options ◽  
3D Cell Culture ◽  
Therapy Resistance ◽  
Ductal Adenocarcinoma ◽  
The Past ◽  
Slow Progress

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.

Survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

2020 ◽  
Vol 21 (4) ◽  
pp. 127-130
Author(s):  
V. U. Rayn ◽  
◽  
A. A. Chernov ◽  
S. O. Zabotkin ◽  
◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Soft Tissues ◽  
Abdominal Cavity ◽  
Survival Rates ◽  
Pancreatic Head ◽  
Ductal Adenocarcinoma ◽  
En Bloc ◽  
Free Survival ◽  
Pancreatic Head Cancer

Aim. To access overall and event-free survival rates in patients after surgical treatment of localized and locally spread pancreatic head cancer. Materials and methods. A single center observational trial was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. Data were collected retrospectively from 2007 to 2019. Patients with resectable tumors were included into the study whose final histology showed pancreatic ductal adenocarcinoma and en-bloc resection. According to the technical facilities and actual clinical protocols all patients received surgical treatment only and were then monitored. Data on progression patterns and survival rates were collected and calculated using Kaplan-Meier survival analysis. Results. Median overall survival (OS) after R0 pancreaticoduodenectomy was 16,8 months (IQR 10,9-23,5). Median progression-free survival was 10,6 mo. (IQR 8,0-20,7). OS in jaundiced patients was 4,9 mo. shorter than in patients without jaundice at the diagnosis (р = 0,011). Patients with serum bilirubin level < 100 μmol/l lived on average 7.2 months longer (p = 0.014). Most frequent sites of primary progression were liver and peritoneum, lungs, bones, lymph nodes of the abdominal cavity / retroperitoneal space, less often metastases were found in the skin and soft tissues. In 21.4% of cases metastases were found in several organs simultaneously with most frequent combination of liver and peritoneum, liver and lungs, lungs and bones. The median survival after progression was 7.1 ± 4.8 months Conclusion. Pancreatic duct adenocarcinoma has a high potential for progression and has therefore poor prognosis. To improve long-term outcomes, it is advisable to apply additional therapeutic options perioperatively.

scholarly journals Pancreatic Ductal Adenocarcinoma (PDAC) Organoids: The Shining Light at the End of the Tunnel for Drug Response Prediction and Personalized Medicine

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2750
Author(s):  
Pierre-Olivier Frappart ◽  
Thomas G. Hofmann
Keyword(s):  
Personalized Medicine ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Response ◽  
Treatment Options ◽  
Response Prediction ◽  
Ductal Adenocarcinoma ◽  
Chemotherapy Treatment ◽  
The Past ◽  
Therapeutic Tools ◽  
And Personalized Medicine

Pancreatic ductal adenocarcinoma (PDAC) represents 90% of pancreatic malignancies. In contrast to many other tumor entities, the prognosis of PDAC has not significantly improved during the past thirty years. Patients are often diagnosed too late, leading to an overall five-year survival rate below 10%. More dramatically, PDAC cases are on the rise and it is expected to become the second leading cause of death by cancer in western countries by 2030. Currently, the use of gemcitabine/nab-paclitaxel or FOLFIRINOX remains the standard chemotherapy treatment but still with limited efficiency. There is an urgent need for the development of early diagnostic and therapeutic tools. To this point, in the past 5 years, organoid technology has emerged as a revolution in the field of PDAC personalized medicine. Here, we are reviewing and discussing the current technical and scientific knowledge on PDAC organoids, their future perspectives, and how they can represent a game change in the fight against PDAC by improving both diagnosis and treatment options.

scholarly journals Comparison of Minimally Invasive versus Open Pancreatoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Propensity Score Matching Analysis

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 982 ◽  
Author(s):  
Jaewoo Kwon ◽  
Ki Byung Song ◽  
Seo Young Park ◽  
Dakyum Shin ◽  
Sarang Hong ◽  
...  
Keyword(s):  
Propensity Score ◽  
Minimally Invasive ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Propensity Score Matching ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
Propensity Score Matching Analysis ◽  
Oncological Outcomes ◽  
Hospital Stays

Background: Few studies have compared perioperative and oncological outcomes between minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDAC). Methods: A retrospective review of patients undergoing MIPD and OPD for PDAC from January 2011 to December 2017 was performed. Perioperative, oncological, and survival outcomes were analyzed before and after propensity score matching (PSM). Results: Data from 1048 patients were evaluated (76 MIPD, 972 OPD). After PSM, 73 patients undergoing MIPD were matched with 219 patients undergoing OPD. Operation times were longer for MIPD than OPD (392 vs. 327 min, p < 0.001). Postoperative hospital stays were shorter for MIPD patients than OPD patients (12.4 vs. 14.2 days, p = 0.040). The rate of overall complications and postoperative pancreatic fistula did not differ between the two groups. Adjuvant treatment rates were higher following MIPD (80.8% vs. 59.8%, p = 0.002). With the exception of perineural invasion, no differences were seen between the two groups in pathological outcomes. The median overall survival and disease-free survival rates did not differ between the groups. Conclusions: MIPD showed shorter postoperative hospital stays and comparable perioperative and oncological outcomes to OPD for selected PDAC patients. Future randomized studies will be required to validate these findings.

scholarly journals The current treatment landscape in the UK for stage III NSCLC

2020 ◽  
Vol 123 (S1) ◽  
pp. 3-9
Author(s):  
Matthew Evison ◽  
Keyword(s):  
Treatment Options ◽  
Survival Rates ◽  
Current Treatment ◽  
Stage Iii ◽  
Diverse Range ◽  
Unresectable Stage ◽  
Radical Therapy ◽  
Modal Treatment ◽  
Stage Iii Nsclc ◽  
The Uk

AbstractFor stage III non-small cell lung cancer (NSCLC), approximately a third of patients survive up to 5 years, with decreasing 5-year survival rates for stage IIIB and stage IIIC disease. Although curable, stage III NSCLC encompasses a diverse range of disease presentation, with an equally complex range of multi-modal treatment options, including systemic and local therapies for distant and local disease control, respectively. This complexity results in a number of challenges for the multi-disciplinary team (MDT) in achieving optimal treatment outcomes for patients. As multi-modality treatment is the preferred treatment strategy for all stage III disease, the focus of this article is the key surgical, chemotherapy and radiotherapy clinical trials as well as guidelines that currently outline radical therapy options for patients with both potentially resectable and unresectable stage III NSCLC.

Chemotherapy use in the treatment of glioblastoma multiforme: Comparing patient characteristics using the National Cancer Data Base (NCDB).

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 305-305
Author(s):  
Christopher J. Inserra ◽  
Nabin Khanal ◽  
Peter T. Silberstein
Keyword(s):  
Glioblastoma Multiforme ◽  
Treatment Options ◽  
Survival Rates ◽  
Patient Characteristics ◽  
The United States ◽  
Current Treatment ◽  
National Cancer Data Base ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Cancer Data

305 Background: Glioblastoma Multiforme (GBM) is the most common and most deadly type of human glioma. Nearly half of all gliomas are diagnosed as GBM at which point the median survival of patients is approximately one year and the two-year survival rates are approximately 10%. Current treatment options for GBM include surgical resection, external beam radiation, and oral temozolomide chemotherapy. However, the patterns of chemotherapy use in GBM as well as the patient characteristics that determine its use have yet to be investigated. Methods: This is a retrospective study of glioblastoma patients (n = 96,966, making this the largest trial ever on glioblastoma) diagnosed between 2000 and 2011 in the NCDB. The NCDB contains nearly 70% of new cancer cases diagnosed in the United States and consists of data from over 1,500 cancer programs across the country. A chi-squared test was used to determine any differences in the characteristics of patients who did or did not receive chemotherapy. Results: Patients who were younger than 70 years of age, male, white, had private/managed insurance, no comorbidities, household income greater than $49,000, were receiving radiation therapy, and diagnosed between 2004 and 2011 were significantly more likely to have received chemotherapy to treat glioblastoma (see Table). Conclusions: Understanding any potential barriers in the use of chemotherapy to treat glioblastoma can help improve its utilization among people of diverse socioeconomic backgrounds. [Table: see text]

scholarly journals MicroRNA-21 Is Induced Early in Pancreatic Ductal Adenocarcinoma Precursor Lesions

2010 ◽  
Vol 56 (4) ◽  
pp. 603-612 ◽  
Author(s):  
Maël Chalret du Rieu ◽  
Jérôme Torrisani ◽  
Janick Selves ◽  
Talal Al Saati ◽  
Anny Souque ◽  
...  
Keyword(s):  
Early Detection ◽  
Mouse Model ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Early Event ◽  
Precursor Lesions ◽  
Tissue Samples ◽  
Ductal Cells

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) has the poorest overall prognosis among gastrointestinal cancers; however, curative resection in early-stage PDAC greatly improves survival rates, indicating the importance of early detection. Because abnormal microRNA production is commonly detected in cancer, we investigated noninvasive precursor pancreatic intraepithelial neoplasia (PanIN) lesions for microRNA production as a potential early biomarker of PDAC. Methods: Pathologists identified and classified ductal lesions. We extracted total RNA from laser-capture microdissected PanIN tissue samples from a conditional KRAS(G12D) mouse model (n = 29) or of human origin (n = 38) (KRAS is v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). MicroRNA production was quantified by quantitative real-time PCR. Internal controls included 5S and U6 RNAs. Results: Production of microRNAs miR-21, miR-205, and miR-200 paralleled PanIN progression in the KRAS(G12D) mouse model, compared with microRNA production in samples of nonpathologic ducts. miR-21 demonstrated the highest relative concentrations in the precursor lesions. Interestingly, miR-205 and miR-21 up-regulation preceded phenotypic changes in the ducts. The production of microRNAs miR-21, miR-221, miR-222, and let-7a increased with human PanIN grade, with peak production occurring in hyperplastic PanIN-2/3 lesions. In situ hybridization analysis indicated miR-21 production to be concentrated in pathologic ductal cells. miR-21 production was regulated by KRAS(G12D) and epidermal growth factor receptor in PDAC-derived cell lines. Conclusions: Aberrant microRNA production is an early event in the development of PanIN. Our findings indicate that miR-21 warrants further investigation as a marker for early detection of PDAC.

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