Cervical cancer (CC) is estimated to account for 8% of the total cancer related mortality in women worldwide, and for who platinum based chemotherapy is just palliative. Hopefully, our group found that HER receptors are good targetable proteins for fighting CC, however, resistance to that drugs remains an enormous clinical problem for other tumor types. Thus, aiming to anticipate the putative molecular mechanisms of resistance, in order to establish predictors of therapy response in CC, herein, it was hypothesized that RKIP tumor suppressor protein could be modulating cells response to HER targeted therapies: first, because of the knowledge that RKIP is downregulated in CC tissues; secondly due of its crucial role in the regulation of important signaling pathways in oncogenesis and therapy prediction, such MAPK pathway. To address our hypothesis, we first recurred to in vitro models that were knocked out for RKIP by using CRISP-Cas9 technology. The genetic manipulated cell lines were used to study the impact of RKIP in HER signalling cascade activation, which was evaluated by western blot. Importantly, the role of RKIP in modulation of response to HER-targeted drugs (AST1306, lapatinib and afatinib) was assessed in the same models by cytotoxic assays. In addition, in vivo CAM assay was used to validate the in vitro findings. Finally, a series of 202 adenocarcinoma human tissues were used to assess RKIP immunohistochemistry to validate some of the findings as well as its prognostic significance. In general, it was found for the first time that even not having a crucial role in intracellular signaling modulation, RKIP and HER receptors showed to be regulating each other, a finding that was consistent in the in vitro models as in the human samples. Additionally, and in contrast to what was expected due to its known negative regulatory role in MAPK pathway, we observed that absence of RKIP expression is a favorable condition for a better response to HER inhibitors. Importantly, these associations were found only for cells that showed to have a RKIP-dependent signaling. Further, we were also able to demonstrate an association between RKIP decrease expression and CC patient’s worse prognosis. In conclusion, the results presented in this thesis provided us important preliminary data that opened us a huge window for future works.