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 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 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.

scholarly journals Comprehensive characterisation of pancreatic ductal adenocarcinoma with microsatellite instability: histology, molecular pathology and clinical implications

Gut ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Claudio Luchini ◽  
Lodewijk A A Brosens ◽  
Laura D Wood ◽  
Deyali Chatterjee ◽  
Jae Il Shin ◽  
...  
Keyword(s):  
Systematic Review ◽  
Microsatellite Instability ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Data ◽  
The Cancer Genome Atlas ◽  
Research Network ◽  
Ductal Adenocarcinoma ◽  
Precision Oncology ◽  
Dna Mismatch ◽  
Molecular Features

ObjectiveRecently, tumours with microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) have gained considerable interest due to the success of immunotherapy in this molecular setting. Here, we aim to clarify clinical-pathological and/or molecular features of this tumour subgroup through a systematic review coupled with a comparative analysis with existing databases, also providing indications for a correct approach to the clinical identification of MSI/dMMR pancreatic ductal adenocarcinoma (PDAC).DesignPubMed, SCOPUS and Embase were searched for studies reporting data on MSI/dMMR in PDAC up to 30 November 2019. Histological and molecular data of MSI/dMMR PDAC were compared with non-MSI/dMMR PDAC and with PDAC reference cohorts (including SEER database and The Cancer Genome Atlas Research Network - TCGA project).ResultsOverall, 34 studies with 8323 patients with PDAC were included in the systematic review. MSI/dMMR demonstrated a very low prevalence in PDAC (around 1%–2%). Compared with conventional PDAC, MSI/dMMR PDAC resulted strongly associated with medullary and mucinous/colloid histology (p<0.01) and with a KRAS/TP53 wild-type molecular background (p<0.01), with more common JAK genes mutations. Data on survival are still unclear.ConclusionPDAC showing typical medullary or mucinous/colloid histology should be routinely examined for MSI/dMMR status using specific tests (immunohistochemistry, followed by MSI-PCR in cases with doubtful results). Next-generation sequencing (NGS) should be adopted either where there is limited tissue or as part of NGS tumour profiling in the context of precision oncology, acknowledging that conventional histology of PDAC may rarely harbour MSI/dMMR.

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.

Modelling the Tumour Microenvironment in Pancreatic Ductal Adenocarcinoma

Pancreatology ◽  
2017 ◽  
Vol 17 (3) ◽  
pp. S4
Author(s):  
Sarah Brumskill ◽  
Lawrence Barrera ◽  
Fiona Campbell ◽  
Chris Halloran ◽  
John Neoptolemos ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma

scholarly journals Extracellular vesicles in pancreatic cancer progression and therapies

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Chao-Hui Chang ◽  
Siim Pauklin
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Delayed Diagnosis ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Ductal Adenocarcinoma ◽  
Cancer Hallmarks ◽  
Pancreatic Cancers

AbstractPancreatic cancer (PC) is one of the leading causes of cancer-related death worldwide due to delayed diagnosis and limited treatments. More than 90% of all pancreatic cancers are pancreatic ductal adenocarcinoma (PDAC). Extensive communication between tumour cells and other cell types in the tumour microenvironment have been identified which regulate cancer hallmarks during pancreatic tumorigenesis via secretory factors and extracellular vesicles (EVs). The EV-capsuled factors not only facilitate tumour growth locally, but also enter circulation and reach distant organs to construct a pre-metastatic niche. In this review, we delineate the key factors in pancreatic ductal adenocarcinoma derived EVs that mediate different tumour processes. Also, we highlight the factors that are related to the crosstalk with cancer stem cells/cancer-initiating cells (CSC/CIC), the subpopulation of cancer cells that can efficiently metastasize and resist currently used chemotherapies. Lastly, we discuss the potential of EV-capsuled factors in early diagnosis and antitumour therapeutic strategies.

scholarly journals The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy

2021 ◽  
Vol 11 ◽  
Author(s):  
Daniel R. Principe ◽  
Patrick W. Underwood ◽  
Murray Korc ◽  
Jose G. Trevino ◽  
Hidayatullah G. Munshi ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Drug Efficacy ◽  
Current Treatment ◽  
Ductal Adenocarcinoma ◽  
Multi Drug Resistance ◽  
Dismal Prognosis ◽  
Treatment Paradigm ◽  
Cytotoxic Therapies ◽  
Poor Outcomes ◽  
Pancreatic Cancer Therapy

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with a median survival time of 10-12 months. Clinically, these poor outcomes are attributed to several factors, including late stage at the time of diagnosis impeding resectability, as well as multi-drug resistance. Despite the high prevalence of drug-resistant phenotypes, nearly all patients are offered chemotherapy leading to modest improvements in postoperative survival. However, chemotherapy is all too often associated with toxicity, and many patients elect for palliative care. In cases of inoperable disease, cytotoxic therapies are less efficacious but still carry the same risk of serious adverse effects, and clinical outcomes remain particularly poor. Here we discuss the current state of pancreatic cancer therapy, both surgical and medical, and emerging factors limiting the efficacy of both. Combined, this review highlights an unmet clinical need to improve our understanding of the mechanisms underlying the poor therapeutic responses seen in patients with PDAC, in hopes of increasing drug efficacy, extending patient survival, and improving quality of life.

scholarly journals Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway

Dermatology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Julia-Tatjana Maul ◽  
Florian Anzengruber ◽  
Curdin Conrad ◽  
Antonio Cozzio ◽  
Peter Häusermann ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Systemic Treatment ◽  
Severe Disease ◽  
Treatment Options ◽  
Maintenance Phase ◽  
Current Treatment ◽  
Induction Phase ◽  
Individual Choice ◽  
Proactive Management ◽  
The Individual

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients’ personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of “classical” mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 μg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4–8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient’s preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis.

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