Nucleic acid-based approaches offer several advantages when compared to treatment with small molecules or proteins. They can be seen as mostly inactive prodrugs, which are activated at the tumor site producing a therapeutically active protein or knocking down a specific target gene. Importantly, nucleic acid targeted delivery systems, preferably also relying in transcriptional targeting, decreasing off-target effects and Inhibitors,research,lifescience,medical toxicity, and permitting a systemic administration otherwise not feasible with a
therapeutic agent with toxic properties. In parallel with new therapeutic nucleic acid tools, the last two decades brought insight into mTOR inhibitor tumorgenesis in general and unveiled a plethora of therapeutic concepts against cancer (Figure Inhibitors,research,lifescience,medical 3). The following paragraphs will deal with different antimelanoma approaches based on nucleic acids. Figure 3 Different strategies used in antitumor nucleic acid approaches. RNA-based strategies are commonly used to downregulate agents that are upregulated to favor cell proliferation or migration, such as Bcl-2. Alternatively, double stranded RNA (dsRNA) mimic … Despite the apparent tumor tolerance, humoral and cellular immune responses are naturally generated against tumor antigens. Hence, whether the tumor grows as a result of stealth and nonrecognition or as the result of escape and immunological shaping ,
Inhibitors,research,lifescience,medical its recognition by the immune system can still be prompted. Indeed, at a later stage, during the progressive Inhibitors,research,lifescience,medical growth phase, tumors may become more immune-activating for varies reasons: damage or disruption of surrounding tissue, generation of reactive oxygen species, upregulation of stress protective factors, or death by necrosis or apoptosis. However, at this stage, it is not known whether the tumor still needs to escape immune recognition, as it is unclear that these immune responses
can cause tumor destruction . Therefore, a number of studies have focused in eliciting earlier and suitable tumor recognition by the immune system. In a nucleic acid therapy context, this transliterates into genetic immunization Inhibitors,research,lifescience,medical or DNA vaccination: the delivery and transcription of a gene encoding antigens or immunestimulatory molecules that elicit PAK6 an immune response. As an example, interleukine-12 (IL-12) has been used and studied in different animal models [104, 105]. IL-12 is originally produced by mononuclear phagocytes and dendritic cells and is responsible for activating NK and CD4+ T cells and inducing the production of high levels of interferon gamma (INF-γ). Interestingly, IL-12 has been described to increase antitumor immune responses [129, 130], and later studies investigated its suitability for a DNA vaccine approach against melanoma . IL-12 effects appeared to be long lasting and efficient against tumor metastases, although not mainly mediated by INF-γ .