Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11

Ukhyun Jo; Yasuhisa Murai; Naoko Takebe; Anish Thomas; Yves Pommier

doi:10.3390/cancers13184601

Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11

Cancers (Basel). 2021 Sep 14;13(18):4601. doi: 10.3390/cancers13184601.

Authors

Ukhyun Jo¹, Yasuhisa Murai^{1

2}, Naoko Takebe³, Anish Thomas¹, Yves Pommier¹

Affiliations

¹ Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892-4264, USA.
² Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
³ Developmental Therapeutics Branch and Division of Cancer Treatment and Diagnosis, NCI, NIH, Bethesda, MD 20892-4264, USA.

Abstract

Precision medicine aims to implement strategies based on the molecular features of tumors and optimized drug delivery to improve cancer diagnosis and treatment. DNA replication is a logical approach because it can be targeted by a broad range of anticancer drugs that are both clinically approved and in development. These drugs increase deleterious replication stress (RepStress); however, how to selectively target and identify the tumors with specific molecular characteristics are unmet clinical needs. Here, we provide background information on the molecular processes of DNA replication and its checkpoints, and discuss how to target replication, checkpoint, and repair pathways with ATR inhibitors and exploit Schlafen 11 (SLFN11) as a predictive biomarker.

Keywords: ATR; Adavoserib; Camptothecin; Ceralasertib; PARP; Rucaparib; berzosertib; cisplatin; niraparib; olaparib; replication stress; schlafen 11; talazoparib; temozolomide.

Publication types

Review

Abstract

Publication types

Grants and funding