The evaluation of response is unquestionably one of the principal difficulties emerging with the more and more frequent use of the new molecularly targeted medicines. As witnessed, initial in gastrointestinal stromal tumors treated with Imatinib and then in the phase trial of Sorafenib in HCC, the traditional response criteria used in Oncology, from WHO to RECIST, which were initially created to assess response to standard chemotherapeutic medicines, are tough to apply to molecularly targeted agents and have a higher threat of underestimating drug activity.
In order to tackle this situation, which will turn into increasingly critical in the near future, some authors have developed new and various recommendations for response evaluation. For Dovitinib , Choi based assessment Elvitegravir on adjustments in tumor density as demonstrated by computed tomography scan, and on those by the EORTC, determined by changes in glucide metabolic process as demonstrated by positron emission tomography with fluorodeoxyglucose. No specific response criteria are however accessible for fusion CT/PET techniques, even though new PET tracers aimed at depicting specific molecular or metabolic pathways are under evaluation.
Since in clinical practice we still depend on inadequate morphologic strategies or not entirely validated functional methods, the want for the advancement of new response evaluation criteria is real and this research area will definitely boom in the up coming handful of years. Regardless of the recent revolution represented by the addition of Sorafenib to our presently poor therapeutic armamentarium and the guarantee proven by experimental treatments, HCC remains an incurable ailment unless it can be handled with surgical radical ablation or transplantation. This lack of curative remedy options is accompanied by the expanding concern of the cost of new molecularly targeted agents, which is particularly important now that monetary sources are restricted. These variables underline the need to recognize truly reputable prognostic and predictive elements, another essential line of study which is undergoing significant progress.
As for Sorafenib, we now know that the volume PARP of basal phosphorylation of ERK a protein downstream of Ras in the MAP kinase pathway, is correlated with PFS in patients treated with this drug. We require to determine and very carefully validate other and far more dependable biomarkers to be in a position to select the patients who could advantage, ornot, from these high-priced treatment options. This will allow us to allocate the scarce resources available in the most appropriate, and accurate, attainable way. Remedy aimed at specific, although often a number of, molecular targets has quickly grown in Oncology, to become the most innovative and promising technique to the therapy of many sound tumors. This strategy also appears really promising in HCC thanks to the improvement of Sorafenib, the first medical therapy confirmed to impact on HCC survival.
Nevertheless, the benefits obtained so far have to be improved. We will have to pursue this aim by greater defining and characterizing DNA-PK the molecular mechanisms Dovitinib underlying carcinogenesis and by as a result producing increasingly particular, active and tolerated molecularly targeted agents. Studies have to be developed that combine distinct agents of this kind with a single yet another and/or with standard chemotherapy or locoregional ablation.
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