Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Knight and colleagues found that low-SES HCT recipients show up-regulation of a conserved transcriptional response to adversity (CTRA) gene expression profile at pretransplant testing. Up-regulated CTRA gene expression was also associated with increased relapse and decreased leukemia-free survival. These results suggest new strategies for mitigating social disparities in cancer treatment outcomes through targeted pharmacologic intervention in the signaling pathways that drive CTRA gene expression.Hatzis and colleagues developed a statistical model to help design the next generation of clinical trials for breast cancer that simultaneously test drug activity in the preoperative (neoadjuvant) treatment setting and the impact on patient survival. Neoadjuvant chemotherapy often completely eradicates the cancer from the breast and lymph nodes, but does not always result in improved survival. The team found higher expected survival benefit for cancers with high risk of recurrence when treated with more effective novel therapies, highlighting the importance of assessing novel treatments in patients that have high risk for recurrence despite current best therapies.Combinations of ibrutinib with anti-CD20 monoclonal antibodies (mAbs) are being evaluated in clinical trials; however, in vitro data identified potentially negative interactions between the two drugs. Skarzynski and colleagues provide conclusive evidence that ibrutinib leads to CD20 downregulation on chronic lymphocytic leukemia (CLL) cells in vivo, resulting in decreased complement-dependent cytotoxicity. Yet, concurrent CD55 (complement inhibitor) downregulation and partial inhibition of mAb-mediated shaving of CD20 from CLL cells by effector cells (trogocytosis) could enhance mAb activity. These positive and negative interactions between ibrutinib and anti-CD20 mAbs could determine the overall therapeutic efficacy of combination therapy and should be investigated further.The site of recurrence affects prognosis in metastatic breast cancer, but the events underlying organ-specificity of metastases are elusive. The authors explored the global transcriptional landscape of clinical breast cancer metastases, unraveling a liver metastasis-selective signature enriched for stromal genes that were predominantly downregulated in liver metastases. Downregulation of the signature was predictive of poor outcome in early breast cancer, with the strongest independent prognostic value within the luminal A subtype. This signature identifies patients with ER-positive breast cancer requiring closer disease monitoring who may be amenable to enrolment into clinical trials investigating novel therapeutics targeting features other than proliferation.