Advances in pancreatic cancer biomarkers

Hasan, Syed; Jacob, Rojymon; Manne, Upender; Paluri, Ravi Kumar

doi:10.4081/oncol.2019.410

Cited by 91 publications

(75 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, there are no predictive biomarkers to inform PDAC response to either Gem/nab-PTX or FOLFIRINOX regimens [31,32], to enhance therapeutic efficacy, or to prevent adverse effects based on the molecular characteristics of the tumors. Based on our findings, K17 may be a candidate predictive biomarker for response to Gem/nab-PTX.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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 and in vivo models of PDAC, spanning human and murine PDAC cells, and orthotopic xenografts, 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 significantly higher sensitivity in K17‐positive compared to K17‐negative PDAC cell lines and animal models. In the clinic, another microtubule inhibitor, paclitaxel (PTX), is used in combination with Gem as a first‐line chemotherapeutic regimen for PDAC. Surprisingly, we found that when combined with Gem, PPT, but not PTX, was synergistic in inhibiting the viability of K17‐expressing PDAC cells. Importantly, in preclinical models, PPT in combination with Gem effectively decreased tumor growth and enhanced the survival of mice bearing K17‐expressing tumors. This provides evidence that PPT and its derivatives could potentially be combined with Gem to enhance treatment efficacy for the ~ 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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…However, all patients had been enrolled in prospective integrated chemo-radiotherapy trials and the 18 F-FDG PET/CT scan had been performed in each case with the same acquisition protocols and uniformly analysed by the same nuclear medicine physicians. Third, a limitation to CA 19-9 serum level evaluation in pancreatic cancer includes false negative results in Lewis negative phenotype (observed in 5–10% of patients with pancreatic cancer) [ 14 ]. In our experience, patient stratification, considering both CA 19-9 levels and 18 F-FDG PET/CT parameters such as MTV and TLG before treatment, is able to effectively predict whether a particular patient with LAPC will or will not have early progression or disease progression during the course of treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a meta-analysis has shown that these metabolic parameters derived from pre-treatment 18 F-FDG PET/CT may play a predictive role for patients with pancreatic cancer [ 13 ]. Moreover, serum carbohydrate antigen (CA) 19-9 has also been studied for its prognostic value [ 14 ]. It is the most common and validated diagnostic tumour marker and is currently being applied in clinical practice for prediction of treatment response and prognosis.…”

Section: Introductionmentioning

confidence: 99%

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer

Fiore

Taralli

Trecca

et al. 2020

Cancers

View full text Add to dashboard Cite

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

show abstract

“…Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancers and is associated with a poor prognosis due to its advanced presentation at diagnosis and limited therapeutic options. The lack of validated predictive markers further complicates this situation [34]. Again, the predictive value of the GALNT14-rs9679162 SNP genotype was examined in PDA patients undergoing surgical resection [35].…”

Section: Pancreatic Ductal Adenocarcinomamentioning

confidence: 99%

GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers

Lin

Yeh

2020

IJMS

View full text Add to dashboard Cite

Members of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family function as the initiating enzymes that catalyze mucin-type O-glycosylation of proteins, and their dysregulated expression can alter cancer cell behaviors such as de novo occurrence, proliferation, migration, metastasis, and drug resistance. Recent studies have demonstrated that one of the family’s members, GALNT14, is aberrantly expressed in multiple cancers and involved in a variety of biological functions. Moreover, the single nucleotide polymorphisms (SNPs) of GALNT14-rs9679162 have been shown to predict therapeutic outcomes in patients with hepatocellular carcinoma as well as several other different types of gastrointestinal cancer. This review summarizes the structural features of GANLT14, its functional roles, and the predictive values of GALNT14 genotypes and enzyme levels in multiple cancers receiving distinct anticancer therapies.

show abstract

Advances in pancreatic cancer biomarkers

Cited by 91 publications

References 95 publications

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

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

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer

GALNT14: An Emerging Marker Capable of Predicting Therapeutic Outcomes in Multiple Cancers

Contact Info

Product

Resources

About