Targeting aberrant replication and DNA repair events for treating breast cancers

Subapriya Rajamanickam, Jun Hyoung Park, Panneerdoss Subbarayalu, Santosh Timilsina, Kaitlyn Bates, Pooja Yadav, Saif S.R. Nirzhor, Vijay Eedunuri, Tabrez A. Mohammad, Kwang Hwa Jung, Benjamin Onyeagucha, Nourhan Abdelfattah, Raymond Benevides, Grace Lee, Yidong Chen, Ratna Vadlamudi, Andrew Brenner, Virginia Kaklamani, Ismail Jatoi, John KuhnRobert Hromas, Yogesh K. Gupta, Benny A. Kaipparettu, Jack L. Arbiser, Manjeet K. Rao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive. In contrast to chemotherapy drugs, systemic delivery of CB suppressed breast cancer growth and metastasis with no toxicity in pre-clinical mouse models. Using PDX and ex vivo explants from estrogen receptor (ER) positive, ER mutant and TNBC patients, we further demonstrated that CB effectively blocks therapy-sensitive and therapy-resistant breast cancer growth without affecting normal breast tissue. Our data provide a strong rationale to develop CB as a viable therapeutic for treating breast cancers.

Original languageEnglish (US)
Article number493
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology
  • Medicine (miscellaneous)

Fingerprint

Dive into the research topics of 'Targeting aberrant replication and DNA repair events for treating breast cancers'. Together they form a unique fingerprint.

Cite this