**2. Oncoproteins in diagnostic: AFP and IGF-I**

### **2.1 AFP**

AFP is present in normal and neoplastic developing tissues [1, 24–26]. The presence of AFP seems to be related to the stage of cell and tissue differentiation. AFP is absent from either undifferentiated or fully differentiated cells [24].

The localization of AFP was compared with that of another oncoprotein—serum albumin, SA. SA-mRNA gave a strong signal in differentiating structures as well as in undifferentiated cell clusters. AFP-mRNA was observed only in differentiating structures; this observation was especially useful in the clinical diagnostic of hepatocarcinoma [4, 27].

During an experiment with teratocarcinoma-bearing mice injected intraperitoneally with J-125 radiolabeled SA and AFP, significant accumulations of both SA and AFP were demonstrated in the tumors, SA being about 3-fold higher than that of AFP after normalization to quantity of uptake in liver. In the case of comparatively studied neuroblastoma presenting only neuroblastic components (different from teratocarcinoma containing both neuroectoblastic and neuroblastic elements), the accumulation of radiolabeled SA and AFP showed relationship 1:1. External *in vivo* photo scanning confirmed this relationship of accumulated radiolabeled proteins in both studied tumors; the last observations were useful for differential diagnosis of tumors [4, 27–36].

AFP may be used to advantage in radio tracing experiments, since this isologous protein is not expected to induce hypersensitivity reactions. On the other hand, and contrary to SA, the extremely low serum levels of AFP in adult individuals should minimize effects due to competition with endogenous protein. This makes AFP a good candidate for tumor biomarker by imaging techniques. The diagnosis and therapies of CNS tumors including neuroblastoma are always a subject of discussion [36–39].

#### **2.2 IGF-I**

Another oncodevelopmental antigen, an insulin like-growth factor, IGF-I [20, 40–43], is present in glioma cells but absent in neuroblastoma cells [18]; neuroblastic cells express IGF-II [27]. These observations permitted to study separately, using IGF-I and IGF-II as the oncoprotein markers, glial and neural tumors [13, 15, 20, 40–42, 44–46].

Comparative studies of AFP, IGF-I, IGF-II presence in neoplastic cells [3, 4, 18] have demonstrated that IGF-I constitutes an essential target for genetic testing. IGF-I, similarly to AFP, is involved in tissue development and differentiation, especially in the development of the nervous system [9, 15, 19, 20, 47–51]. According to

**61**

*Oncoproteins Targeting: Antibodies, Antisense, Triple-helix. Case of Anti IGF-I Cancer…*

and tumors [5, 9, 13, 39, 68, 69]. Diagnosis and treatment should logically be

related, at first using IGF-I gene testing for diagnosis [13, 21, 70], and then targeting IGF-I gene through special therapy, such as cancer gene therapy, especially therapy

To target an oncoprotein directly on protein level, the strategy of antibodies was

The treatment of any cancer, especially hepatocarcinoma, demands a permanent perfusion, *per vena porta*, of anti AFP antibodies. The arrest of perfusion has produced the reappearance of cancer. Similar observation has been made when using

The only possibility was to stop the synthesis of the oncoprotein on the translation or on the transcription level of the concerned gene, and directly in the cancer cells. This hypothesis and our knowledge of chemistry was an epistemological problem, pointed out by Mosquera "how to integrate the knowledge of chemistry

As to glioma malignant tumor, glioblastoma (the mortality remains close to 100%), new or proposed therapies are based generally either on immune treatment or on immuno-gene strategies [75, 76]. In order to define new therapies, the different techniques for inhibitors [9], and the anti-gene strategy (either antisense, AS, or

The AS technology [77, 78] has permitted us to establish new and successful gene therapy strategies targeting glioma's growth factors [11, 79] and have now been introduced into clinical trials. Other recently introduced technologies include those of triple helix, TH [80–83], as well as potentially useful siRNA [84, 85] and miRNA (microRNA) [82, 83, 86, 87]. The role of 21–23 mer double-stranded RNA (siRNA) in the silencing of genes is strongly similar to that of the TH DNA mechanism, which also involves 23 mer RNA [81]. Whether or not siRNA technology or miRNA knockdown will supplant the AS and TH oligodeoxynucleotide approaches remains in question at this time [83, 85, 87–90]. AS methodology is currently being stan-

As to TH strategy, the oligonucleotides are targeted to double stranded DNA containing polypurine-polypyrimidine sequences that readily form triple helixes. The studies of triple helix strategy have shown that an RNA strand containing a 23-nucleotide (nt) oligopurine sequence [80, 86, 87] may be capable of forming triple helix structures with an oligopurine-oligopyrimidine sequence of the IGF-I gene as well in cultured rat C6 glioma as in rat CNS-1 glioma, and in mouse PCC-4 cells [86]. Although we cannot exclude other mechanisms, triple helix formation remains the most plausible possibility for the inhibition of IGF-I gene expression [86]. The arrest of IGF-I synthesis suggests that the RNA strand, which forms the

triple helix, TH, approaches) were investigated [61] (**Figure 1**).

dardized to be largely used in clinical trials [18, 89].

triple helix, has inhibited gene transcription in glioma cells.

explored. Cancers treated by use of antibodies was in general not efficient.

Baserga [43], IGF-I is one of the most important growth factors related to normal

The elements of IGF-I related transduction pathway (IRS/PI3K-PKC/PDK1/AKT-Bcl2/GSK3/GS) [55, 56] were also considered as targets for diagnostic [9, 55, 57–66]. The relationship between IGF-I and IGF binding proteins are being introduced in clinical diagnostics as one of the indicators of precancerous development [67]. IGF-I becomes useful in molecular diagnostic of neonatal CNS malformations

*DOI: http://dx.doi.org/10.5772/intechopen.82548*

and neoplastic differentiation [50, 52–54].

**3. IGF-I and anti-gene immunotherapy**

antibodies against growth factors.

with technique" [74].

**3.1 Protein, translation and transcription levels**

of gliomas [11, 22, 71–73].

*Oncoproteins Targeting: Antibodies, Antisense, Triple-helix. Case of Anti IGF-I Cancer… DOI: http://dx.doi.org/10.5772/intechopen.82548*

Baserga [43], IGF-I is one of the most important growth factors related to normal and neoplastic differentiation [50, 52–54].

The elements of IGF-I related transduction pathway (IRS/PI3K-PKC/PDK1/AKT-Bcl2/GSK3/GS) [55, 56] were also considered as targets for diagnostic [9, 55, 57–66]. The relationship between IGF-I and IGF binding proteins are being introduced in clinical diagnostics as one of the indicators of precancerous development [67].

IGF-I becomes useful in molecular diagnostic of neonatal CNS malformations and tumors [5, 9, 13, 39, 68, 69]. Diagnosis and treatment should logically be related, at first using IGF-I gene testing for diagnosis [13, 21, 70], and then targeting IGF-I gene through special therapy, such as cancer gene therapy, especially therapy of gliomas [11, 22, 71–73].
