Table 1.
Schematic summary of potential glycolytic targets in Pancreatic ductal adenocarcinoma (PDA) therapy.
| Target | Overexpression | Clinical Outcome | Targeting Approach | Correlation with Immune Response | |||
|---|---|---|---|---|---|---|---|
| Cell Line | Tissue | Survival | PD/M | CT Resistance | |||
| KRAS/TP53 | PCR [11] IHC [11,12] RNAseq [13] |
↓ [11,14] | ↑ M [11] | KRAS interference [11] KRAS/p53 peptide vaccination [11,15,16,17,18] RT11-i [19] |
Chemokine secretion, macrophage recruitment and lymphocyte and myeloid cell infiltration [11] | ||
| GLUT1 | qPCR [20] WB [20,21] |
RNAseq [15,16] IHC [17,18] |
↓ [22] | * ↑ M [21] | [22] | GLUT1 silencing [21] TWIST1 silencing [23] Apigenin [24,25] PON2 [26] |
Positive correlation with PD1+ TILs [18] High GLUT1 expression in activated Tregs [27] |
| HK2 | qPCR [28] WB [28,29] |
mRNA [30] IHC [30,31,32] Microarray [33] |
↓ [29,31] ↑ [32] |
* ↑ M [28] | [28] | HK2 silencing [28] IKA [34] |
|
| ALDOA | IHC [35] | ↓ [35] | * ↑ M [35] | ALDOA silencing [35] TDZD-8 [36] TX-2098 [37] |
Circulating auto-Ab to ALDOA [10] | ||
| TPI | RNAseq [13] | RNAseq [13] IHC [38] |
↓ [13,38] | [13,39] | Circulating auto-Ab to TPI [9,10] |
||
| GAPDH | mRNA [40] WB [40] |
2-DE [41] IHC [41] mRNA [40] WB [40] |
↓ [39] | * ↑ M [42] | [39] | 2-DG [43] P1DG [44] AXP3009 [45] Genipin [45,46] KA [47] |
Humoral and cellular responses to GAPDH [10,48] |
| FOXM1 | Microarray [49] mRNA [50] IHC [51] WB [51] |
↓ [50,52] | ↑ PD [53] ↑ M [50,53] |
[51] * [54] |
Genistein [55] FOXM1 siRNA [56,57] FOXM1 RNA interference [58] USP5 inhibition [59] Thiazole antibiotic [60] MG115 and MG132 [61,62] 5,7 Dimethoxyflavone [63] |
DC maturation [64,65] T cell proliferation [65] |
|
| PGK1 | 2-DE [66] | mRNA [67] 2-DE [66] |
↓ [67,68] | ↑ M [69] | [67] | Circulating auto-Ab [10,66,68] High concentration of PGK1 in serum [70] |
|
| LDHA | WB [71,72,73,74] qPCR [72] |
Microarray [71] IHC [71,74,75] mRNA [72] WB [72] |
↓ [71] | ↑ PD [75] | LDHA RNA interference [72] LDHA siRNA [73,74] EGCG [76] 2-DG [76] Graviola [77] FX11 [78,79] |
Negative correlation with CD8+ TIL [71] * Low cytotoxic NK activity [80] * High MDSC activity [80] |
|
| ENO1 | mRNA [40] WB [40] Microarray [81] Flow cytometry [82] |
2-DE [41] mRNA [40] WB [40] Microarray [81] IHC [83] |
↓ [39,83,84] | * ↑ M [85] | [39,84] | ENO1 DNA vaccination alone or in combination with GEM [10,86] ENO1 silencing [82,85] Anti-ENO1 mAb [82,87] PhAH [88] ENO1 knockdown [88] Citrullinated ENO1 peptides [89] |
Increased level of anti-ENO1 Ab before and after GEM treatment [9,10,90,91] Increased T cell response in vitro and in vivo [81,91] Increased level of ENO1 in plasma patients [83] ENO1-specific Th17 and Treg response [92] |
| PKM2 | WB [71,93,94] qPCR [94] |
IHC [31,71,93,94] ↓ IHC [95,96] Microarray [97] Oncomine database [97] |
↓ [31,71,97,98] | ↑ M [31,99] * ↑ PD [98] |
[98] | PKM2 knockdown [94,99,100,101] PKM2 silencing [97] 2-DG [102,103] Shikonin [103] Betulinic acid and thymoquinone and GEM [104] |
Increased level of anti-PKM2 Ab before and after GEM treatment [10] Negative correlation with CD8+ TIL [71] |
CT—chemotherapy; PD—progressive disease; M—metastasis; *—preclinical mouse model; Ab—antibody; IHC—immunohistochemistry; WB—Western blot; qPCR—quantitative PCR; 2-DE—2-dimensional electrophoresis.