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Immunotherapy with ipilimumab improves the survival of only around 20% of patients with metastatic melanoma. To explore reliable markers for the prediction of clinical outcome, Gebhardt and colleagues analyzed myeloid cells and related inflammatory factors in the peripheral blood of treated patients. Response to the therapy was associated with an early increase in eosinophil count, whereas nonresponders showed elevated amounts and function of circulating monocytic myeloid-derived suppressor cells as well as increased serum levels of S100A8/A9 and HMGB1. These novel complex predictive markers could help to identify metastatic melanoma patients who benefit from the ipilimumab therapy.The identification of biomarkers that early predicts the chemosensitivity of triple-negative breast cancers (TNBC) to standard neoadjuvant chemotherapy (NAC) is an important issue. Indeed, poorly responding women may be good candidates for emerging targeted therapy. Humbert and colleagues studied the predictive value of 18FDG-PET compared with clinicobiologic markers of TNBC. The authors demonstrated that combining positive EGFR status and a low 18FDG-PET tumor response after the first cycle of NAC can predict residual invasive carcinoma at the end of treatment. Multicenter trials using PET-guided treatment strategies are now necessary to evaluate the benefit of early therapeutic changes in poorly responding women.Clinical studies have demonstrated that tumor relapse after radiotherapy occurs preferentially in tumor areas with high 18F-fluorodeoxyglucose (FDG) uptake. To test the therapeutic gain from radiation dose escalation to the potentially radioresistant tumor subvolumes with high FDG, Trani and colleagues employed dose painting approaches in rat rhabdomyosarcoma: targeted dose escalation and dose redistribution. Although dose escalation to high FDG uptake was not superior to the same dose increase in low FDG uptake subvolumes, dose redistribution was even detrimental, consistent with the hypothesis that tumor response depends on the minimum intratumoral dose. These findings provide important information for the design of clinical trials.In HER2/ERBB2-amplified gastrointestinal tumors, concomitant HER2 targeting by trastuzumab antibody and the reversible inhibitor lapatinib is more effective than either agent alone. The mechanisms of this cooperation are unknown. Leto and colleagues found that trastuzumab and lapatinib complement each other to induce sustained neutralization of HER2 and its signaling partners HER3 and EGFR. This durable inhibition, which accounts for massive tumor shrinkage, is recapitulated by monotherapy with the HER2 irreversible inhibitor afatinib. These results provide functional evidence for the collaborative activity of trastuzumab and lapatinib and propose afatinib treatment as a means to diversify therapeutic opportunities in HER2-amplified gastrointestinal carcinomas.