**5.1 Estimation of clinical trials with success outcome on advanced pancreatic cancer**

Total, we found 10 publications where the author declares the successful outcome on the treatment of APC from 2011 to 2019, **Table 2**. These clinical trials recruited 1080 patients with APC (611 male and 469 female). The average overall survival month is 11.62 and progress-free survival month is 10.79. Briefly, Lutz et al. tests the GVAX pancreatic cancer vaccine via GPI biomarkers The OS and PFS approach got the highest point, 24.8 and 17.3, respectively Similarly, Phan et al. tested the pazopanib hydrochloride via VEGF biomarkers. This approach had a higher OS and PFS points. Survival months are 25 and 14.4. Furthermore, Hong et al. disclosed the capecitabine may put the OS and PFS to 17.3 and 10.4 survival months; the remain studies presented similar results, the OS and PFS were lower than 10 months.


#### **Table 1.**

*Potential biomarkers used in advanced pancreatic cancer.*


**5.2 Estimation of clinical trials with the neutral outcome on advanced**

*What Are the New Challenges of the Current Cancer Biomarkers?*

*DOI: http://dx.doi.org/10.5772/intechopen.89976*

For details please see **Table 3**. Averagely the OS is 16.6 months and PFS is 9 months in neutral studies. For example, Jean in 2008 reported gemcitabine plus AG-013736 achieved better OS and PFS (6.9 and 4.2) than gemcitabine

**5.3 Estimation of clinical trials with the failed outcome on advanced**

Here are three studies clarified neural results in OS and PFS result, ranged from 2008 to 2016, totally recruited 229 APC patients (121 male and 108 female).

Regarding the failed outcomes, there are 14 studies ranged from 2011 to 2018, recruited 2448 APC patients (1385 male and 1063 female) for clinical trials. For details please see **Table 1**. Averagely the OS is 8.25 months and PFS is 4.39 months. It is evident that Faivre et al. in 2016 tested sunitinib malate to treat APC and achieved 38.6 months of OS and 12.6 months of PFS. However, Brian reported that hydroxychloroquine cures APC, unfortunately, there were 1.8 months both in OS and PFS negativity. Even though many combination tests, the benefit for APC

VEGF is a highly specific vascular endothelial cell mitogen and an angiogenic factor associated with platelet-derived growth factor (PDGF) structure. It is also known as vascular permeability factor (VPF), due to its permeabilization of blood vessels [24]. It is a subfamily of growth factors and belongs to a family of plateletderived growth factors of cystine knot growth factor. VEGF is divided into the following groups: VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and placental growth factor. VEGF binds to three transmembrane receptors (VEGFR1, VEGFR2 and VEGFR3). This receptor initiates downstream signaling through intracellular tyrosine kinase activity [25]. In fact, VEGF family members are playing an important role in the physiological angiogenesis of adults. Like wound healing,

Activation of the VEGF/VEGF receptor (VEGFR) axis may trigger multiple signaling networks. Consequently, this may lead to endothelial cell survival, mitosis, migration and differentiation, vascular permeability and mobilization of endothelial progenitor cells (EPCs) from the bone marrow into the peripheral circulation [27]. On ligand binding, VEGFR-2 dimerization results in kinase activation and autophosphorylation of tyrosine residues. Activation of PKC may stimulate the Raf/MEK/ERK pathway, which accelerates the cell proliferation. Ca2+ mobilization and PKC activation are playing the key role in signaling events for VEGF-A-induced vascular permeability through activation of endothelial nitric oxide

The sword has double sides. VEGF participates in the pathogenesis of cancer, proliferative retinopathy and rheumatoid arthritis [29]. Its antibodies have shown therapeutic potential to inhibit tumor growth in vivo by inhibiting tumor-induced angiogenesis [30]. VEGF overexpression is associated with a variety of tumor progression and poor prognosis, including colorectal cancer [31], pancreatic cancer [32],

**pancreatic cancer**

**pancreatic cancer**

**6. Different perspectives on biomarkers**

**6.1 Vascular endothelial growth factor, VEGF**

ovulation and pregnancy [26].

synthase activity [28].

**133**

single used.

patient is low.

#### **Table 2.**

*Clinical trials with a successful outcome on pancreatic cancer.*


**Table 3.**

*Clinical trial with neutral outcomes on pancreatic cancer.*

**Year Author N M F Drug OS PFS Biomarkers**

docetaxel;

gemcitabine

cancer

Vaccine

docetaxel

2014 Ban [17] 33 30 3 Belotaxel; belloxa 10.9 3.6 Double-strand breaks in

gemcitabine;

Gemcitabine

gemcitabine;

gemcitabine

gemcitabine;

gemcitabine

hydrochloride

hydrochloride

leucovorin

fluorouracil;

leucovorin

**Year Author N M F Drug OS PFS Biomarkers** 2008 Spano [21] 69 35 34 Gemcitabine 5.6 3.7 VEGF

2015 Hobday [22] 58 29 29 Bevacizumab; temsirolimus 34 13.2 VEGF 2016 Stein [23] 37 21 16 MPC modified FOLFIRINOX 10.2 6.1 DPD

34 16 18 Gemcitabine; AG-013736 6.9 4.2

31 20 11 LAPC modified FOLFIRINOX 26.6 17.8

71 44 27 TH-303 with

74 42 32 TH-304 with

20 12 8 Pazopanib

149 81 68 5 Fluorouracil;

117 69 48 MM-398; 5

2011 Raymond [14] 86 42 44 Sunitinib 9 30 VEGF 85 40 45 Sunitinib 21 51 2013 Hosein [15] 19 9 10 Abraxane 7.3 1.7 SPARC

7.4 5.8 TP

24.8 17.3 GPI

5.3 3.7 TP

6.9 3.6 Severe hypoxia

25 14.4 VEGF

8.7 5.6

9.2 6

18.5 12.2

4.2 1.6

6.2 3.1

151 87 64 MM-398 4.9 2.7 Topoisomerase I inhibitor

DNA

Intracellular reductases

2011 Hill [12] 21 8 13 Capecitabine;

*Current Cancer Treatment*

2011 Lutz [13] 60 37 23 GVAX pancreatic

2014 Soares [16] 43 21 22 Capecitabine;

2014 Borad [18] 69 40 29 TH-302 with

2015 Phan [19] 32 22 10 Pazopanib

*Clinical trials with a successful outcome on pancreatic cancer.*

*Clinical trial with neutral outcomes on pancreatic cancer.*

2019 Wang-Gillam [20]

**Table 2.**

**Table 3.**

**132**
