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aberrant glycosylation, one of the hallmarks of cancer, occurs due to numerous modifications that result
in the formation of various glycosylated residues such as CA 19-9/(SIa) which has emerged as a potential
biomarker [15-17] .

To emphasize the clinical relevance of this molecule, the survival rates of PDAC patients have been shown
to be inversely related to the levels of CA 19-9 [18,19] . In these reports, increased levels of CA 19-9 were found
to be associated with unresectable lesions or more numbers of advanced tumours, which indicates a poor
prognosis for PDAC patients [18,19] . Given the importance of this biomarker, studies conducted by Isacoff et al.
[20]
have demonstrated that patients with normal levels of CA 19-9 (i.e., 36 U/mL or less) during the initial
course of therapy had higher median survival rate compared to those who had elevated CA 19-9 levels (more
than 36 U/mL). Furthermore, the median survival of PDAC patients on therapy who had a reduction in CA
19-9 levels by 90% was significantly longer than those patients with a less than 90% reduction in the level
[20]
of this biomarker . However, since CA 19-9 is a tumour-associated but not a tumour-specific antigen, its
implications are not pathognomonic for pancreatic cancer. It is known to be synthesized by the gall bladder,
epithelial cells of the pancreas, stomach, and biliary ducts, which explains the increased level of CA 19-9 in
the benign as well as advanced conditions of many malignancies [21-24] . In this current review, we highlight
the recent updates, and therapeutic potential, of CA 19-9, with an emphasis on experimental and clinical
studies, as well as its importance as a prognostic biomarker in pancreatic cancer.

IMPLICATION OF CA 19-9 IN PDAC
In vivo studies
[27]
Several studies have highlighted the role of CA 19-9 in PDAC models [25,26] . Wagner et al. conducted
an in vivo study using three orthotopic xenograft mouse models to examine the efficacy of targeted
immunocytokine L19-IL-2 in pancreatic cancer with the goal of assessing CA 19-9 as a biomarker for
tumour progression when treated with L19-IL-2. Treatment with L19-IL-2 resulted in a significant
reduction in the serum levels of CA 19-9, but no changes were observed with either IL-2 or L19 alone
treatments. In contrast, there was a significant increase in the serum levels of CA 19-9 in the untreated
control group of mice. This indicates a significant correlation between the serum levels of CA 19-9 and
tumour volume of PDAC, and that a positive response of L19-IL-2 on CA 19-9 was observed against
[27]
PDAC . Overall, these results corroborate the crucial role of CA 19-9 as a biomarker to assess the
treatment responses for PDAC [Table 1].

Human studies
Applicability of CA 19-9 levels to determine therapeutic and prognostic responses in PDAC
There have been numerous studies investigating the clinical relevance of CA 19-9 in pancreatic cancer,
and to define its applicability in predicting either the responses or resistance to various treatments [28-30] . A
summary of these investigations is given in Table 2. Kieler et al. evaluated CA 19-9 levels in response
[28]
to chemotherapy with nanoliposome irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) as a
second-line treatment for PDAC and compared it with oxaliplatin plus fluoropyrimidines. The findings
revealed that at the start of therapy, the median progression-free survival (PFS) was significantly longer
in patients who received nal-IRI plus 5 FU/LV compared to the median PFS in patients treated with
oxaliplatin plus fluoropyrimidines. In addition, the median overall survival (OS) of patients with CA 19-9
levels over 772.8 kU/L receiving nal-IRI plus 5 FU/LV was significantly higher compared to those who were
treated with oxaliplatin plus fluoropyrimidines. This study indicated the effectiveness of nal-IRI plus 5-FU/
LV treatment in PDAC when compared with oxaliplatin plus fluoropyrimidines, and that increased CA 19-9
response was associated with better therapeutic outcomes.

[29]
In another report, Li et al. performed a prospective study to determine the therapeutic response to
modified-FOLFIRINOX and correlated it with CA19-9 levels in patients with metastatic PDAC. The study