Antibody to CD137 activated by extracellular adenosine triphosphate is tumor selective and broadly effective in vivo without systemic immune activation

Agonistic antibodies targeting CD137 have been clinically unsuccessful due to systemic toxicity. Since conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigen, we exploited extracellular adenosine triphosphate (exATP), which is a hallmark of the tumor microenvironment and highly elevated in solid tumors, as a broadly tumor…

A Comprehensive Review and Perspective on Anticancer Mechanisms of Withaferin A in Breast Cancer

Withaferin A (hereafter abbreviated as WA) is a promising anticancer steroidal lactone abundant in a medicinal plant ( Withania somnifera ) native to Asia. The root/leaf extract of Withania somnifera , which belongs to the Solanaceae family, continues to be included in the Ayurvedic medicine formulations of alternative medicine practice. Numerous chemicals are detectable in the root/leaf extract…

Multidimensional analyses of donor memory-like NK cells reveal new associations with response after adoptive immunotherapy for leukemia

NK cells are an emerging cancer cellular therapy and potent mediators of anti-tumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in acute myeloid leukemia (AML) patients. However, the dynamic changes in phenotype that occur after NK cell transfer that impact patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates…

The Folate Cycle Enzyme MTHFR is a Critical Regulator of Cell Response to MYC-Targeting Therapies.

Deciphering the impact of metabolic intervention on response to anticancer therapy may elucidate a path toward improved clinical responses. Here, we identify amino acid-related pathways connected to the folate cycle whose activation predicts sensitivity to MYC-targeting therapies in acute myeloid leukemia (AML). We establish that folate restriction and deficiency of the rate-limiting folate cycle…

BI-3406, a potent and selective SOS1::KRAS interaction inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition

KRAS is the most frequently mutated driver of pancreatic, colorectal, and non-small cell lung cancers. Direct KRAS blockade has proven challenging and inhibition of a key downstream effector pathway, the RAF-MEK-ERK cascade, has shown limited success due to activation of feedback networks that keep the pathway in check. We hypothesized that inhibiting SOS1, a KRAS activator and important feedback…

Prognostic and predictive impact of circulating tumor DNA in patients with advanced cancers treated with immune checkpoint blockade

The utility of circulating tumor DNA (ctDNA) as a biomarker in patients with advanced cancers receiving immunotherapy is uncertain. We therefore analyzed pretreatment (n=978) and on-treatment (n=171) ctDNA samples across 16 advanced stage tumor types from three phase I/II trials of durvalumab (± anti-CTLA-4 therapy tremelimumab). Higher pretreatment variant allele frequencies (VAF) were…

Three-Dimensional Printing for Preoperative Planning and Pedicle Screw Placement in Adult Spinal Deformity: A Systematic Review – Cesar D. Lopez, Venkat Boddapati, Nathan J. Lee, Marc D. Dyrszka, Zeeshan M. Sardar, Ronald A. Lehman, Lawrence G. Lenke, 2020

Study Design: Systematic review. Objectives: This current systematic review seeks to identify current applications and surgical outcomes for 3-dimensional print…

Low Colorectal Cancer Screening Uptake and Persistent Disparities in an Underserved Urban Population

Colorectal cancer screening has increased substantially in New York City in recent years. However, screening uptake measured by telephone surveys may not fully capture rates among underserved populations. We measured screening completion within 1 year of a primary care visit among previously unscreened patients in a large urban safety-net hospital and identified sociodemographic and…

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Characteristics of breast ducts in normal risk and high risk women and their relationship to ductal cytologic atypia.

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal risk (NR) or at high-risk (HR) for sporadic breast cancer. Breast ductal cells…