Supplementary Tables 1-6. Table 1 shows the correlation between immunohistochemical factors and clinicopathological data, Table 2: Univariate analyses of patients characteristics and IHC factors to disease-free survival, Table 3: Multivariate analysis for training and validation sets: clinicopathological variables, Table 4: Multivariate Analyses: OS for patients according to the nodal status, Table 5: Interaction between adjuvant therapy and biomarkers, Table 6: Stromal index and patients' outcomes

Supplementary Figures 1-3. Figure 1: Flow chart of patients thought the study for the 3 cohorts of patients. Figure 2: Caption : Photomicrographs showing examples of PDAC. Figure 3: Cumulative overall survival according to the combined expression of Shh and Gli1

Abstract Background This analysis evaluated the morbimortality and the potential benefit of esophagectomy for cancer in elderly patients. Methods Patients who underwent esophagectomy for EC were divided into elderly (≥70 years) and nonelderly (<70 years) groups. The groups were compared regarding patient and tumor characteristics, postoperative morbimortality, and disease‐free, overall and cancer‐specific survival. Results Sixty‐one patients were classified into elderly, and 187 into nonelderly groups. The elderly were characterized by a higher rate of WHO score (p < 0.0001), higher cardiac (p < 0.004) and renal (p < 0.023) comorbidities. The rate of neoadjuvant therapy and especially of neoadjuvant CRT was significantly lower in elderly patients (p < 0.018 and p < 0.007). Operative morbidity was also higher in this group (p < 0.024). The 30‐ and 90‐day mortality was 8.2 and 11.5%, respectively in elderly patients and 0.5 and 3.2% in nonelderly patients (p < 0.004 and p < 0.012). This 90‐day mortality decreased when specific surgery‐related deaths were taken into consideration. OS and DFS were significantly better in the nonelderly group (p < 0.003 and p < 0.005) while no difference was observed for cancer‐specific survival (CSS). Conclusion No difference in CSS was observed. Although elderly patients with EC had higher postoperative morbimortality, the age should not be a criterion whether to perform, or not to perform, esophagectomy. This decision must be based on the balance between the patient's general condition and aggressive disease.

Undifferentiated carcinoma of the pancreas is an aggressive but rare tumor for which several other terms have been used to describe its histological appearance. In addition, as osteoclast-like giant cells may accompany undifferentiated carcinoma of the pancreas, the WHO Classification distinguishes undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) from plain undifferentiated carcinoma since there are a few histopathological and clinical differences. UC-OGC was initially thought to be associated with worse prognosis compared to invasive ductal pancreatic adenocarcinoma, since it is often unresectable at diagnosis and tends to recur rapidly even if completely resected. When true UC-OGGs are carefully dissected out from other anaplastic carcinomas, it becomes, however, clear that UC-OGCs do have more indolent behavior, especially the pure UC-OGCs. This mini-review summarizes the current knowledge on UC-OGC.

'Mind-body' debates assume that better brain-body associations are healthy. This study examined whether degree of associations between a neurophysiological vagal nerve index and peripheral disease biomarkers predict prognosis in pancreatic cancer (PC) and multiple sclerosis (MS). Sample 1 included 272 patients with advanced PC. Sample 2 included 118 patients with MS. We measured the vagal nerve index heart rate variability (HRV) derived from electrocardiograms. We examined associations between HRV and patients' peripheral disease biomarkers: CA19-9 in PC and neurofilament light chain (NFL) in MS. Associations between HRV and each biomarker were examined separately in patients who survived or died (PC), and in those with and without relapse during 12 months (MS). In PC, HRV was significantly inversely related to the tumor marker CA19-9 in patients who later survived (r = -0.44, p < 0.05) but not in those who died (r = 0.10, NS). In MS, HRV was significantly and inversely related to NFL only in those who did not relapse (r = -0.25, p < 0.05), but not in those who relapsed (r = -0.05, NS). The degree of association between a neurophysiological vagal marker and peripheral disease biomarkers has prognostic value in two distinct diseases.

Gemcitabine is still one of the standard chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine uptake into tumor cells is mainly through the human equilibrative nucleoside transport 1 (hENT1). It was therefore proposed as a potential predictive biomarker of gemcitabine efficacy but reports are conflicting, with an important heterogeneity in methods to assess hENT1 expression. A multicenter cohort of 471 patients with a resected PDAC was used to assess simultaneously the predictive value of the 2 best described hENT1 antibodies (10D7G2 and SP120). Three additional antibodies and the predictive value of hENT1 mRNA were also tested on 251 and 302 patients, respectively. hENT1 expression was assessed in 54 patients with matched primary tumors and metastases samples. The 10D7G2 clone was the only hENT1 antibody whose high expression was associated with a prolonged progression free survival and overall survival in patients who received adjuvant gemcitabine. hENT1 mRNA level was also predictive of gemcitabine benefit. hENT1 status was concordant in 83% of the cases with the best concordance in synchronous metastases. The 10D7G2 clone has the best predictive value of gemcitabine benefit in PDAC patients. Since it is not commercially available, hENT1 mRNA level could represent an alternative to assess hENT1 status.

e15622 Background: The REACHIN trial met its primary endpoint of improving PFS for patients with biliary tract cancer (BTC) treated with regorafenib (R) as compared to placebo (P): Median (m) PFS for R was 3.0 months (mo) (95% CI: 2.3-4.9) and 1.5 mo (95% CI : 1.2-2.0) for P with an HR= 0.49 (95% CI: 0.29-0.81), p=0.005 (Demols A et al, ASCO-GI 2019, Abstr 345). We exploratory analyzed the benefit of R according to tumor location: intra-hepatic (ICC), extra-hepatic (ECC), gallbladder (GB) or peri-hilar (PH). Methods: Tumor locations were recorded at randomization of patients in REACHIN (NCT02162914), a multicenter double-blinded P-controlled randomized phase II study to evaluate the safety and efficacy of R in patients with locally advanced (non resectable) and metastatic histologically proven BTC, progressing after gemcitabine-platinum. We analyzed mPFS according to tumor location and their respective 95% CI. Results: 66 patients were randomized and the mPFS data are summarized in the table. Conclusions: Most of the patients had ICC location (64%). The mPFS in the P arm is similar according to the tumor location. Despite its exploratory value and the small number of patients per tumor location, R seems superior to P in ICC, GB and PH. Data in ECC are not conclusive. Additional biomarkers (FGFR, NGS analysis) are ongoing and will be presented at the meeting. Clinical trial information: NCT02162914. [Table: see text]

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.

PURPOSE:To prospectively assess chemotherapy-induced changes in pancreatic ductal adenocarcinoma (PDA) with diffusion-weighted (DW)-MR quantitative metrics, including apparent diffusion coefficient (ADC) and histogram-derived parameters, compared with RECIST 1.1. METHODS:24 patients underwent DW-MR at baseline, week-2 and week-8 after chemotherapy initiation. Tumour diameter was assessed on T2-weighted images. Regions-of-interest (ROI) were drawn on ADC map for ROI-ADC. Volume segmentation (b = 1000 s/mm2 images) provided DW-volume and histogram-derived diffusion parameters (H-ADC, H-D and H-PF). All variables and their relative change were compared to baseline or between responders and non-responders. Discriminant analysis was performed. RESULTS:15/24 patients were responders. RECIST 1.1 correctly characterized 6/15 responders at week-8. At week-2, in responders DW-volume decreased (P = .002); ROI-ADC mean H-D increased (P = .047; P = .048;). The 25th percentile H-D increased in responders and decreased in non-responders (P = .016; P = .048). At week-8 in responders DW-volume decreased and ROI-ADC mean, 25th, 50th, 75th percentiles of H-ADC and H-D increased (P < .05). No changes were observed in non-responders (P > .05). At week-2, 25th percentile of H-D and H-PF relative change correctly classified 20/24 patients (P = .003); at week-8, DW-volume relative change correctly classified 22/24 patients (P < .0001). CONCLUSIONS:ROI-ADC, DW-volume and histogram-derived diffusion parameters are more accurate to categorize responding and non-responding PDA patients treated with chemotherapy compared with RECIST 1.1.

BACKGROUND & AIMS:Genomic studies have revealed subtypes of pancreatic ductal adenocarcinoma (PDA) based on their molecular features, but different studies have reported different classification systems. It is a challenge to obtain high-quality, freshly frozen tissue for clinical analysis and determination of PDA subtypes. We aimed to redefine subtypes of PDA using a large number of formalin-fixed and paraffin-embedded PDA samples, which are more amenable to routine clinical evaluation. METHODS:We collected PDA samples from 309 consecutive patients who underwent surgery from September 1996 through December 2010 at 4 academic hospitals in Europe; nontumor tissue samples were not included. Samples were formalin fixed and paraffin embedded. DNA and RNA were isolated; gene expression, targeted DNA sequencing, and immunohistochemical analyses were performed. We used independent component analysis to deconvolute normal, tumor, and microenvironment transcriptome patterns in samples. We devised classification systems from an unsupervised analysis using a consensus clustering approach of our data set after removing normal contamination components. We associated subtypes with overall survival and disease-free survival of patients using Cox proportional hazards regression with estimation of hazard ratios and 95% confidence interval. We used The Cancer Genome Consortium and International Cancer Genome Consortium PDA data sets as validation cohorts. RESULTS:We validated the previously reported basal-like and classical tumor-specific subtypes of PDAs. We identified features of the PDA, including microenvironment gene expression patterns, that allowed tumors to be categorized into 5 subtypes, called pure basal like, stroma activated, desmoplastic, pure classical, and immune classical. These PDA subtypes have features of cancer cells and immune cells that could be targeted by pharmacologic agents. Tumor subtypes were associated with patient outcomes, based on analysis of our data set and the International Cancer Genome Consortium and The Cancer Genome Consortium PDA data sets. We also observed an exocrine signal associated with acinar cell contamination (from pancreatic tissue). CONCLUSIONS:We identified a classification system based on gene expression analysis of formalin-fixed PDA samples. We identified 5 PDA subtypes, based on features of cancer cells and the tumor microenvironment. This system might be used to select therapies and predict patient outcomes. We found evidence that the previously reported exocrine-like (called ADEX) tumor subtype resulted from contamination with pancreatic acinar cells. ArrayExpress accession number: E-MTAB-6134.

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis. Virtually all PDA are characterized by mutation of four driver genes: KRAS, TP53, CDKN2A and SMAD4 and a long tail of rarely mutated genes. Application of targeted next-generation sequencing (NGS) has entered clinical routine for colon, lung and other cancers. Among patients with resected PDA, usefulness, applicability and prognostic significance of NGS results are still a matter of debate. Aims: To evaluate: 1) the alterations of the 4 main driver genes and patient outcomes after resection 2) the usefulness of targeted NGS in finding targetable alterations. Methods: We analyzed DNA alterations in FFPE tumors among 279 patients with curatively resected PDA who were treated at 4 Academic Hospitals (Franco-Belgian consortium). Sequencing libraries were prepared using a 50 genes panel (Ion AmpliSeqTM Cancer HotSpot Panel v2, Life Technologies). Sequencing was performed on an Ion ProtonTM System using an Ion PITM Sequencing 200 Kit and an Ion PITM Chip Kit v3 (Life Technologies). Associations of driver gene alterations with disease-free survival (DFS) and overall survival (OS) were evaluated using Cox proportional hazards regression with estimation of hazard ratios (HRs) and 95% CIs and adjusted for age, sex, tumor characteristics and institution. Results: Of the 279 patients analyzed, 163 (58.4%) were men and 116 (41.6%) were women, with a median age of 64.59 (36.9-87.5) years. KRAS, TP53, CDKN2A and SMAD 4 were mutated in 246, 193, 45 and 44 patients respectively. Patients with KRAS mutant tumors did not have worse DFS (median [95% CI], 12.2 [11.35-14.6] months) and OS (23.9 [21.1-30.1] months) compared to patients with KRAS wild-type tumors (DFS, 14.3 [9.64-19.4] months; OS, 31.8 [19.4-53.5] months). The mutational status of TP53 or SMAD4 was not associated with DFS or OS as well. CDKN2A mutations were associated with a lower OS (mutation: 20.5 [14.6-33.0] versus wild-type 26.5 [21.9-33.3] months OS, log-rank <1% HR 1.65 [1.124-2.436]) but not to a lower DFS. Patients had slightly worse DFS and OS if they had a greater number of altered driver genes. Compared with patients with 0 to 2 altered genes, those with 3 to 4 altered genes had worse DFS (HR, 1.377 [95% CI, 1-1.89; P=.05]) and OS (HR, 1.476 [95% CI, 1.04-2.09; P= .028]). For some patients (n=27, 9.68%), we found mutations that could be targeted (i.e PTEN, STK11, GNAS, PIK3CA, FLT3, BRAF, IDH1/2, RET, FGFR3, KIT, AKT1). Conclusions: Analysis of the four main driver gene alterations introduces weak prognostic information with little added clinical value. However, application of NGS in resected PDA is quite feasible and is able to find targetable mutations. KRAS and CDKN2A deserve future attention for targeting specific mutations Citation Format: Francesco Puleo, Rémy Nicolle, Yuna Blum, Jérôme Cros, Nabila Elarouci, Denis Franchimont, Jacques Devière, Aurélien de Reyniès, Pierre Laurent-Puig, Jean-Baptiste Bachet, Raphaël Maréchal, Jean-Luc Van Laethem. Clinical application and potential usefulness of targeted next-generation sequencing on resected pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4603.

Background The vagus nerve may slow tumor progression because it inhibits inflammation. This study examined the relationship between a new vagal neuroimmunomodulation (NIM) index and survival in fatal cancers. Method We retroactively derived markers of vagal nerve activity indexed by heart rate variability (HRV), specifically the root mean square of successive differences (RMSSD), from patients' electrocardiograms near diagnosis. The NIM index was the ratio of RMSSD to C-reactive protein levels (RMSSD/CRP). Sample 1 included 202 Belgian patients with advanced pancreatic cancer (PC), while sample 2 included 71 Belgian patients with non-small cell lung cancer (NSCLC). In both samples, we examined the overall survival, while in sample 2, we additionally examined the survival time in deceased patients. Results In PC patients, in a multivariate Cox regression controlling for confounders, the NIM index had a protective relative risk (RR) of 0.68 and 95% confidence interval (95% CI) of 0.51–0.92. In NSCLC patients, the NIM index also had a protective RR of 0.53 and 95% CI of 0.32–0.88. Finally, in NSCLC, patients with a higher NIM index survived more days (475.2) than those with lower NIM (285.1) (p < 0.05). Conclusions The NIM index, reflecting vagal modulation of inflammation, may be a new independent prognostic biomarker in fatal cancers.

Background: Renal toxicity induced by cisplatin (CisPt) is a clinical issue in patients with or without chronic kidney disease (CKD). Proximal tubular injury can result in acute kidney injury (AKI), which may compromise the course of chemotherapy and the prognosis. The purpose of this study was to investigate the time course of urinary markers of acute tubulotoxicity and to assess the usefulness of such monitoring in a routine clinical setting. Methods: This work is an open prospective pilot study carried out among 23 patients receiving a platinum-based chemotherapy. Individual comorbidities, plasma parameters of kidney function (urea, creatinine) and estimated glomerular filtration rate were registered. Urinary excretion of leucine aminopeptidase, neutrophil gelatinase-associated lipocalin, cystatin C, liver fatty acid-binding protein and interleukin-18 were monitored during successive chemotherapy cycles. Episodes of AKI were identified according to KDIGO (Kidney Disease Improving Global Outcomes) 2012 guidelines. Results: A total of 28 patients were recruited; among them 23 agreed to be part of the study, of whom 18 received CisPt and 5 carbo-or oxaliplatin. Of the 18 CisPt patients, 12 had a preexisting CKD. Sixteen AKI episodes were observed in 13 patients receiving CisPt with a pejorative evolution in seven cases (partial recovery of the renal function); a transient but dramatic increase in urinary biomarkers was observed 3h after chemotherapy initiation, whereas plasma creatinine rise appeared 72h after the end of CisPt treatment. Identified precipitating factors included: dehydration due to lack of fluid intake or diuretic use, exposure to high CisPt doses, regular use of nonsteroidal anti-inflammatory drugs and/or iodinated contrast agents and sepsis. Conclusion: Even if numerous precipitating factors could be avoided, the monitoring of urinary markers seemed helpful for the early detection of subclinical AKI induced during CisPt chemotherapy.

Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians' tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians' decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer. First, we demonstrated that, in PDA, PAP/REG3A is produced by inflamed acinar cells from the peritumoral microenvironment and then enhances the migratory and invasive abilities of cancer cells. More specifically, using perineural ex vivo assays we revealed that PAP/REG3A favors PNI through activation of the JAK/STAT signaling pathway in cancer cells. Finally, we analyzed the level of PAP/REG3A in blood from healthy donors or patients with PDA from three independent cohorts. Patients with high levels of PAP/REG3A had overall shorter survival as well as poor surgical outcomes with reduced disease-free survival. Our study provides a rationale for using the PAP/REG3A level as a biomarker to improve pancreatic cancer prognosis. It also suggests that therapeutic targeting of PAP/REG3A activity in PDA could limit tumor cell aggressiveness and PNI.

BACKGROUND:There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4) as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC).METHODS:Using immunohistochemistry (IHC) and tissue microarray (TMA), we assessed the expression patterns of DLL4, Notch1 and Notch3 in 151 patients from two independent cohorts of resected PDAC. We investigated the prognostic and the predictive significance of these proteins.RESULTS:High IHC DLL4 expression in cancer cells was associated with worse overall survival (OS) and disease-free survival (DFS) than low DLL4 expression (median OS: 12.9 vs 30.4 months, P=0.004 and median DFS: 8.8 vs 17.4 months, P=0.02). High DLL4 expression remained a significant negative prognostic factor in multivariate analysis (HR for OS: 2.1, P=0.02 and HR for DFS: 2.0, P=0.02). Low DLL4 abundance was associated with a longer OS-only for patients who received an adjuvant gemcitabine-based chemotherapy (P<0.001) but not for patients who did not receive gemcitabine (P=0.72). Furthermore, the interaction test for adjuvant gemcitabine therapy was statistically significant (P<0.001). The validating cohort recapitulated the findings of the training cohort.CONCLUSIONS:Low DLL4 abundance in tumour cells may predict the benefit from adjuvant gemcitabine therapy after PDAC resection.

Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims.After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins.Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long-term survival, but the best treatment options should be determined in prospective randomised studies.Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nabpaclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies. (C) 2016 Elsevier Ltd. All rights reserved.

Definitive radiochemotherapy (dRCT) in locally advanced esophageal cancer is associated with a high rate of loco‐regional recurrence. In this condition, salvage esophagectomy may be considered as a therapeutic option. The aim of this analysis is to evaluate the feasibility and the morbi‐mortality of this strategy.

either wedged into an intercalated duct cell line or the intercalated duct cell line branching off from that intercalated duct, and there was scant intercellular space without a PAM-stained membrane in portions between endocrine cells and adjacent acinar cells, as well as those intercalated duct cells. The interface portions with scant intercellular space between peripheral islet cells and adjacent peripheral exocrine glands noted in LM observations were also observed with TEM, which revealed a lack of space and no basement membrane (Figs. 1E–G).

Solid tumors often display chemotherapy resistance. Pancreatic ductal adenocarcinoma (PDAC) is the archetype of resistant tumors as current chemotherapies are inefficient. The tumor stroma and extracellular matrix (ECM) are key contributors to PDAC aggressiveness and to limiting the efficacy of chemotherapy. Lysyl oxidase (LOX) family members mediate collagen cross-linking and thus promote ECM stiffening. Our data demonstrate increased LOX, LOXL1, and LOXL2 expression in PDAC, and that the level of fibrillar collagen, which is directly dependent of LOX family activity, is an independent predictive biomarker of adjuvant "Gemcitabine-based chemotherapy" benefit. Experimentally in mice, increased LOX family activity through LOXL2 promotes chemoresistance. This effect of LOX family activity seems to be due to decreased gemcitabine intra-tumoral diffusion. This observation might be explained by increased fibrillar collagen and decreased vessel size observed in tumors with increased LOX family activity. In conclusion, our data support that LOX family activity is both a novel target to improve chemotherapy as well as a novel biomarker to predict gemcitabine benefit in PDAC. Beyond the PDAC, it is possible that targeting LOX family activity might improve efficacy of chemotherapies against different kinds of solid tumors.