Targeting replication stress in cancer therapy
Replication stress is a major cause of genomic instability and a crucial vulnerability of
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …
Combining targeted DNA repair inhibition and immune-oncology approaches for enhanced tumor control
K Concannon, BB Morris, CM Gay, LA Byers - Molecular cell, 2023 - cell.com
Targeted therapy and immunotherapy have revolutionized cancer treatment. However, the
ability of cancer to evade the immune system remains a major barrier for effective treatment …
ability of cancer to evade the immune system remains a major barrier for effective treatment …
Mechanistic understanding of human SLFN11
FJ Metzner, SJ Wenzl, M Kugler, S Krebs… - Nature …, 2022 - nature.com
Abstract Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA
endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in …
endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in …
Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a phase I study
TA Yap, MG Krebs, S Postel-Vinay, A El-Khouiery… - Clinical Cancer …, 2021 - AACR
Purpose: This study reports the safety, tolerability, MTD, recommended phase II dose
(RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of …
(RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of …
Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial
Summary Background The Wee1 (WEE1hu) inhibitor adavosertib and gemcitabine have
shown preclinical synergy and promising activity in early phase clinical trials. We aimed to …
shown preclinical synergy and promising activity in early phase clinical trials. We aimed to …
Design and preclinical evaluation of a novel B7-H4–directed antibody–drug conjugate, AZD8205, alone and in combination with the PARP1-selective inhibitor …
Purpose: We evaluated the activity of AZD8205, a B7-H4–directed antibody–drug conjugate
(ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination …
(ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination …
Structural and biochemical characterization of human Schlafen 5
FJ Metzner, E Huber, KP Hopfner… - Nucleic Acids …, 2022 - academic.oup.com
The Schlafen family belongs to the interferon-stimulated genes and its members are
involved in cell cycle regulation, T cell quiescence, inhibition of viral replication, DNA-repair …
involved in cell cycle regulation, T cell quiescence, inhibition of viral replication, DNA-repair …
Phosphorylation-mediated conformational change regulates human SLFN11
Abstract Human Schlafen 11 (SLFN11) is sensitizing cells to DNA damaging agents by
irreversibly blocking stalled replication forks, making it a potential predictive biomarker in …
irreversibly blocking stalled replication forks, making it a potential predictive biomarker in …
A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers
B Zhang, K Ramkumar, RJ Cardnell, CM Gay… - British journal of …, 2021 - nature.com
DNA-damaging agents exploit increased genomic instability, a hallmark of cancer. Recently,
inhibitors targeting the DNA damage response (DDR) pathways, such as PARP inhibitors …
inhibitors targeting the DNA damage response (DDR) pathways, such as PARP inhibitors …
Tuft cell-like carcinomas: Novel cancer subsets present in multiple organs sharing a unique gene expression signature
Background Tuft cells are chemosensory epithelial cells playing a role in innate immunity.
Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax …
Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax …