Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

McGuigan, Andrew; Kelly, Paul; Turkington, Richard; Jones, Claire; Coleman, Helen; McCain, R Stephen

doi:10.3748/wjg.v24.i43.4846

Cited by 1,356 publications

(1,218 citation statements)

References 110 publications

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“…Ninety percentage of pancreatic tumors are pancreatic ductal adenocarcinoma (PDAC) while 3-5% are neuroendocrine tumors (PNETs) (191). Smoking, heavy alcohol consumption, obesity, H. pylori infection, and chronic pancreatitis are risk factors (192). Prognosis is incredibly poor, approximately 70% of patients will succumb to the disease in the first year (193).…”

Section: Pancreatic Cancermentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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Section: Pancreatic Cancermentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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“…The "good" quality studies on salivary biomarkers and lung cancer are those demonstrating an association with EGFR, the 5 mRNA, microbiota and cytokines (8)(9)(10)(11) (45). Similarly, pancreatic carcinoma is insidious, very aggressive and in most cases diagnosed at a very late stage, being associated to a very poor prognosis (46). With regard to gastric cancer 7 studies were included in the present review (15)(16)(17)25,(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review

Meleti¹,

Cassi²,

Vescovi³

et al. 2020

Med Oral

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Background: Saliva evaluation could be a possible alternative to blood and/or tissue analyses, for researching specific molecules associated to the presence of systemic diseases and malignancies. The present systematic review has been designed in order to answer to the question "are there significant associations between specific salivary biomarkers and diagnosis of systemic diseases or malignancies?". Materials and Methods: The Preferred Reporting Item for Systematic Reviews and Meta-analysis (PRISMA) statement was used to guide the review. The combinations of "saliva" and "systemic diseases" or "diagnosis" or "biomarkers" or "cancers" or "carcinoma" or "tumors", were used to search Medline, Scopus and Web of Science databases. Endpoint of research has been set at May 2019. Studies were classified into 3 groups according to the type of disease investigated for diagnosis: 1) malignant tumors; 2) neurologic diseases and 3) inflammatory/metabolic/cardiovascular diseases. Assessment of quality has been assigned according to a series of questions proposed by the National Institute of Health. Level of evidence was assessed using the categories proposed in the Oxford Center for Evidence-Based medicine (CEMB) levels for diagnosis (2011).

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“…To evaluate whether PPT might enhance Gem-mediated cytotoxicity and determine if the combined effect is synergistic, additive or antagonistic, we measured cell viability by treating with 9 increasing doses of the combination of Gem and PPT at fixed ratios (1:1 in L3.6 cells and 37.5:1 in MIA PaCa-2 and KPC cells, based on their IC50 values of Gem and PPT, according to established protocols26). We found that K17-expressing cells had significantly lower cell viability under the same doses compared with non-K17-expressing cells ( Fig.…”

Section: Targeting Microtubule Disassembly Rather Than Microtubule Asmentioning

confidence: 99%

An unbiased high-throughput drug screen reveals a potential therapeutic vulnerability in the most lethal molecular subtype of pancreatic cancer

Pan

Otsuka

Sridharan

et al. 2019

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related deaths in the United States by 2020, due in part to innate resistance to widely used chemotherapeutic agents and limited knowledge about key molecular factors that drive tumor aggression. We previously reported a novel negative prognostic biomarker, keratin 17 (K17), whose overexpression in cancer results in shortened patient survival. In this study, we aimed to determine the predictive value of K17 and explore the therapeutic vulnerability in K17-expressing PDAC, using an unbiased high-throughput drug screen. Patient-derived data analysis showed that K17 expression correlates with resistance to Gemcitabine (Gem). In multiple in vitro models of PDAC, spanning human and murine PDAC cells, we determined that the expression of K17 results in a more than twofold increase in resistance to Gem and 5-fluorouracil, key components of current standard-of-care chemotherapeutic regimens. Furthermore, through an unbiased drug screen, we discovered that Podophyllotoxin (PPT), a microtubule inhibitor, showed at least two-fold higher sensitivity in K17expressing compared to K17-negative PDAC cells. In the clinic, another microtubule inhibitor, Paclitaxel (PTX), is used in combination with Gem as a first line chemotherapeutic regimen for pancreatic, breast, lung, and ovarian cancer. Surprisingly, we found that when combined with Gem, PPT but not PTX, was synergistic in inhibiting the viability of K17-expressing PDAC cells. This provides evidence that PPT or its derivatives could potentially be combined with Gem to enhance treatment efficacy for the approximately 50% of PDACs that express high levels of K17. In summary, we reported that K17 is a novel target for developing a biomarker-based personalized treatment for PDAC.3 4 2. Methods 2.1. Predictive-value analyses from patient-derived samples K17 mRNA expression levels of PDAC cases were acquired from the Australian Pancreatic Cancer Genome Initiative (APGI)13. K17 mRNA expression and survival were evaluated in 94 PDAC patients that were treated with adjuvant Gem alone or received no treatment. Based on the established cutoff of the maximum likelihood fit of a Cox proportional hazard model15, we applied the 76th percentile of mRNA expression to categorize patients into high-K17 versus low-K17 groups. Overall survival in high-versus low-K17 mRNA was determined using the Kaplan-Meier method, calculated from the date of diagnosis to the date of death. Patients still alive at the last follow-up were censored. Prognostic and predictive analyses were performed based on the criteria described by Ballman18. Adjusting for potential confounders, a multivariate analysis was performed by Cox proportional hazard regression. Statistical significance was set at p<0.05 and analysis was done using SAS 9.4 (SAS Institute) and GraphPad Prism 7 (Graph Pad Software). Compounds testedGem (purity > 99%), 5-FU (purity > 99%), Podophyllotoxin (PPT, purity > 99%), Taxol (PTX, purity > 95%), Mitoxant...

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Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes

Cited by 1,356 publications

References 110 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Salivary biomarkers for diagnosis of systemic diseases and malignant tumors. A systematic review

An unbiased high-throughput drug screen reveals a potential therapeutic vulnerability in the most lethal molecular subtype of pancreatic cancer

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