Importantly, we found that approximately of mCRC non-responders do not harbor mutations of KRAS, BRAF, PIK3CA nor loss of PTEN expression and we propose to define these tumors as “quadruple negative”. The lack of response in quadruple negative patients may be due to multiple reasons including but not restricted to: a) the limited sensitivity of current sequencing methods in detecting point mutations in DNA extracted from FFPE tumors ; b) the oncogenic deregulation of the same four genes by mechanism other then mutations ; c) the occurrence of alterations in other key elements of the EGFR-dependent signal cascade ; and d) the presence of genetic alterations in tyrosine kinase receptors other than EGFR, providing an alternate pathway of survival and/or proliferation. Further molecular dissections of the EGFR-initiated oncogenic signaling cascade are likely to be helpful in improving the tailoring of EGFR targeted therapies. Overall, our results underscore the relevance of using molecular-based algorithms to shift the treatment of solid tumors into the era of personalized cancer medicine. Failures in communication among healthcare professionals remain a major root cause of adverse events. Open and respectful communication about safety rule violations, potential mistakes and each other��s fallibilities is an essential resource to protect patients from harm, and to learn from errors as an individual, as a team, and as an organization. However, HCPs often report hesitating to speak up about their safety-related concerns. For example, in a recent study among HCPs in labor and delivery, only a minority of Liensinine-Perchlorate doctors, nurses and midwives reported sharing their full patient safety concerns with the errant colleague. Organizational culture, personality traits and the interactions between them have been identified as important determinants of the propensity to speak up. Sibiricose-A5 Despite these stable factors, situation-specific conditions such as the clinical setting or the nature of the safety threat seem to influence the ad-hoc decision whether and how to voice concerns. Willingness to speak up appears to fluctuate strongly in relation to context and social relationships between involved health care professionals.