Interventions Reducing Racial/Ethnic Disparities Across the Cancer Care Continuum: A Scoping Review

https://openworks.mdanderson.org/sumexp23/1126/thumbnail.jp

PARP Inhibitors for Breast Cancer: Germline <em>BRCA1/2</em> and Beyond

Poly-adenosine diphosphate ribose polymerase (PARP) inhibitors (PARPi) are approved for BRCA1/2 carriers with HER2-negative breast cancer in the adjuvant setting with a high risk of recurrence as well as the metastatic setting. However, the indications for PARPi are broader for patients with other cancer types (e.g., prostate and ovarian cancer), involving additional biomarkers (e.g., ATM, PALB2, and CHEK) and genomic instability scores. Herein, we summarize the data on PARPi and breast cancer and discuss their use beyond BRCA carriers

Off-Pump Triple Coronary Artery Bypass Grafting in a Patient with Situs Inversus Totalis: Case Presentation and a Brief Review of the Brazilian and the International Experiences

Abstract A 76-year-old man with situs inversus totalis underwent a successful off-pump three-vessel coronary artery bypass surgery. The postoperative course was uneventful, and the patient was discharged 8 days later. At 9-month follow-up a coronary computed tomography angiography confirmed the viability of all of the grafts, and one year after the operation the patient remained asymptomatic. It comprises the fifth Brazilian case of a coronary surgery in a patient with situs inversus totalis and the first one of the country of a coronary artery bypass surgery without the use of the cardiopulmonary bypass in this condition

E-learning for neurosurgeons:Getting the most from the new web tools

As open access resource, the role of Internet has been increasing in our professional life. There are several emergent new tools that can facilitate and make it more efficient to get accurate and reliable information. In this article, we discuss how we can manage to get the most from these new instruments, like blogs, Facebook, Twitter, and LinkedIn, in order to improve clinical practice. With good sense and some caution, these can turn to be of valuable help in our careers

Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers

Purpose: The identification of patients with homologous recombination deficiency (HRD) beyond BRCA1/2 mutations is an urgent task, as they may benefit from PARP inhibitors. We have previously developed a method to detect mutational signature 3 (Sig3), termed SigMA, associated with HRD from clinical panel sequencing data, that is able to reliably detect HRD from the limited sequencing data derived from gene-focused panel sequencing. Experimental Design: We apply this method to patients from two independent datasets: (i) high-grade serous ovarian cancer and triple-negative breast cancer (TNBC) from a phase Ib trial of the PARP inhibitor olaparib in combination with the PI3K inhibitor buparlisib (BKM120; NCT01623349), and (ii) TNBC patients who received neoadjuvant olaparib in the phase II PETREMAC trial (NCT02624973). Results: We find that Sig3 as detected by SigMA is positively associated with improved progression-free survival and objective responses. In addition, comparison of Sig3 detection in panel and exome-sequencing data from the same patient samples demonstrated highly concordant results and superior performance in comparison with the genomic instability score. Conclusions: Our analyses demonstrate that HRD can be detected reliably from panel-sequencing data that are obtained as part of routine clinical care, and that this approach can identify patients beyond those with germline BRCA1/2mut who might benefit from PARP inhibitors. Prospective clinical utility testing is warranted.publishedVersio

PARP-inhibition reprograms macrophages toward an anti-tumor phenotype

Poly(ADP)ribosylation inhibitors (PARPis) are toxic to cancer cells with homologous recombination (HR) deficiency but not to HR-proficient cells in the tumor microenvironment (TME), including tumor-associated macrophages (TAMs). As TAMs can promote or inhibit tumor growth, we set out to examine the effects of PARP inhibition on TAMs in BRCA1-related breast cancer (BC). The PARPi olaparib causes reprogramming of TAMs toward higher cytotoxicity and phagocytosis. A PARPi-related surge in NAD+ increases glycolysis, blunts oxidative phosphorylation, and induces reverse mitochondrial electron transport (RET) with an increase in reactive oxygen species (ROS) and transcriptional reprogramming. This reprogramming occurs in the absence or presence of PARP1 or PARP2 and is partially recapitulated by addition of NAD derivative methyl-nicotinamide (MNA). In vivo and ex vivo, the effect of olaparib on TAMs contributes to the anti-tumor efficacy of the PARPi. In vivo blockade of the “don’t-eat-me signal” with CD47 antibodies in combination with olaparib improves outcomes in a BRCA1-related BC model.publishedVersio