Mutation of the tumor suppressor gene, TP53, is associated with abysmal survival outcomes in acute myeloid leukemia (AML). Although it is the most commonly mutated gene in cancer, its occurrence is observed in only 5–10% of de novo AML, and in 30% of therapy related AML (t-AML). TP53 mutation serves as a prognostic marker of poor response to standard-of-care chemotherapy, particularly in t-AML and AML with complex cytogenetics. In light of a poor response to traditional chemotherapy and only a modest improvement in outcome with hypomethylation-based interventions, allogenic stem cell transplant is routinely recommended in these cases, albeit with a response that is often short lived. Despite being frequently mutated across the cancer spectrum, progress and enthusiasm for the development of p53 targeted therapeutic interventions is lacking and to date there is no approved drug that mitigates the effects of TP53 mutation. There is a mounting body of evidence indicating that p53 mutants differ in functionality and form from typical AML cases and subsequently display inconsistent responses to therapy at the cellular level. Understanding this pathobiological activity is imperative to the development of effective therapeutic strategies. This review aims to provide a comprehensive understanding of the effects of TP53 on the hematopoietic system, to describe its varying degree of functionality in tumor suppression, and to illustrate the need for the adoption of personalized therapeutic strategies to target distinct classes of the p53 mutation in AML management.

In metastatic CRC, the addition of bevacizumab to oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and the rate of thrombocytopenia.

Metastatic pancreatic cancer carries a poor prognosis, with median survival on the order of several months. There is evidence that combining gemcitabine with either erlotinib or cisplatin may be superior to single agent gemcitabine in patients with good performance (PS 0-1). We retrospectively compared outcomes of patients treated with either the three drug regimen of gemcitabine, cisplatin, and erlotinib (GCE) or the doublet of gemcitabine and cisplatin (GC) in order to assess the potential benefit of erlotinib. We also evaluated the role of erlotinib among smokers and non-smokers. We retrospectively analyzed 145 patients who presented between 2006 and 2009 with previously untreated metastatic pancreatic cancer initially treated at the M.D. Anderson cancer center with either GC or GCE. Information on tumor characteristics and overall survival time (OS) was collected by medical record review. Kaplan-Meier curves were used to estimate OS. Log rank tests were used to compare OS between groups. The Cox proportional hazards regression model was used to evaluate the ability of patient prognostic variables or treatment group to predict OS. A total of 71 patients were treated with GC, while 74 were treated with GCE. Cox analyses found no significant difference in overall survival (median 5.5 vs. 8.0 months, respectively, p-value=0.1). Small sampling numbers may have contributed to this result. One year survival was 23 % in the GCE group and 13 % in the GC group. Patients with poor performance status (PS=2-3) had worse survival as compared to patients with better performance status (PS=0-1, p=0.001). As in earlier studies, patients treated with more lines of therapy tended to have better survival (p <0.0001), and CA19-9 was found to be a significant predictor for OS (p=0.001). No statistical evidence of a survival difference was found between smokers and non-smokers in both treatment groups (p=0.72). In conclusion, though there was a trend towards improved survival with the addition of erlotinib to gemcitabine and cisplatin, this does not reach statistical significance.

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy.