The Biology of Breast Cancer Initiation

Breast Cancer susceptibility genes in Ductal Carcinoma In Situ (DCIS) progression

Overview

This project focuses on the earliest stages of breast cancer development, particularly the premalignant stage known as Ductal Carcinoma In Situ (DCIS). Although most DCIS lesions never progress to invasive disease, current clinical practice cannot reliably distinguish indolent lesions from those with malignant potential. We seek to uncover the molecular mechanisms that enable rare populations of premalignant cells to survive, adapt to stressful microenvironments, and initiate breast cancer.

We are particularly interested in breast cancer susceptibility genes identified through genome-wide association studies (GWAS), many of which remain poorly characterized despite their strong links to disease risk. Rather than acting as classical oncogenes, we hypothesize that some of these genes are activated only transiently in rare premalignant cells, inducing persistent changes in metabolism, stress tolerance, and cell fate that promote cancer initiation.

To address these questions, we combine bioinformatic analyses with molecular studies of human DCIS specimens, organoid cultures, and genetically engineered mouse models. Our goal is to identify the cellular states and molecular pathways that determine whether premalignant lesions remain benign or progress to invasive breast cancer.

Ultimately, this work aims to improve early diagnosis, reduce overtreatment of DCIS, and identify new strategies for breast cancer prevention.

Relevant Publications

2026

IL-6R blockade with tocilizumab disrupts pericyte-and tumor cell-driven IL-6/STAT3 signaling, enhancing docetaxel efficacy in ER+ breast cancer

Roza Kamila Przanowska, Jacky Gomez-Villa, Victoria J. Liu, Natalia Antonides-Jensen, Lavanya Visvabharathy, John C. Alverdy, Sonia L. Hernandez, Samantha S. Yee

openRxiv  ·  30 Jan 2026  ·  doi:10.64898/2026.01.29.702661

2025

Fast, flexible, learning-free organoid quantification and tracking with OrganoSeg2

Cameron J. Wells, Najwa Labban, Shayna L. Showalter, Roza K. Przanowska, Kevin Janes

openRxiv  ·  16 Aug 2025  ·  doi:10.1101/2025.08.13.669694

A 36-base hairpin within lncRNA DRAIC, which is modulated by alternative splicing, interacts with the IKKα coiled-coil domain and inhibits NF-κB and tumor cell phenotypes

Xiaoxiao Hao, Yuechuan Chen, Divya Sahu, Róża K. Przanowska, Mujawar Aaiyas, Chase A. Weidmann, Isaac Nardi, Kevin M. Weeks, Anindya Dutta

Journal of Biological Chemistry  ·  01 Jun 2025  ·  doi:10.1016/j.jbc.2025.110172

DNA replication in primary hepatocytes without the six-subunit ORC

Róża K Przanowska, Yuechuan Chen, Takayuki-Okano Uchida, Etsuko Shibata, Xiaoxiao Hao, …, Piotr Przanowski, Anthony Trimboli, Yoshiyuki Shibata, Gustavo Leone, Anindya Dutta

eLife  ·  30 Apr 2025  ·  doi:10.7554/eLife.102915.3

DNA replication in primary hepatocytes without the six-subunit ORC

Róża K Przanowska, Yuechuan Chen, Takayuki-Okano Uchida, Etsuko Shibata, Xiaoxiao Hao, …, Piotr Przanowski, Anthony Trimboli, Yoshiyuki Shibata, Gustavo Leone, Anindya Dutta

eLife  ·  30 Apr 2025  ·  doi:10.7554/eLife.102915

2024

Patient-derived response estimates from zero-passage organoids of luminal breast cancer

Róża K. Przanowska, Najwa Labban, Piotr Przanowski, Russell B. Hawes, Kristen A. Atkins, Shayna L. Showalter, Kevin A. Janes

Breast Cancer Research  ·  31 Dec 2024  ·  doi:10.1186/s13058-024-01931-5

Patient-derived response estimates from zero-passage organoids of luminal breast cancer

Roza Przanowska, Najwa Labban, Piotr Przanowski, Russell Hawes, Kristen Atkins, Shayna Showalter, Kevin Janes

openRxiv  ·  27 Mar 2024  ·  doi:10.1101/2024.03.24.586432

2023

ANKLE1 cleaves mitochondrial DNA and contributes to cancer risk by promoting apoptosis resistance and metabolic dysregulation

Piotr Przanowski, Róża K. Przanowska, Michael J. Guertin

Communications Biology  ·  01 Mar 2023  ·  doi:10.1038/s42003-023-04611-w

Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis

Arun B. Dutta, Daniel S. Lank, Roza K. Przanowska, Piotr Przanowski, Lixin Wang, Bao Nguyen, Ninad M. Walavalkar, Fabiana M. Duarte, Michael J. Guertin

Genome Research  ·  21 Feb 2023  ·  doi:10.1101/gr.277559.122

2022

Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors

Roza K. Przanowska, Chase A. Weidmann, Shekhar Saha, Magdalena A. Cichewicz, Kate N. Jensen, …, Patrick S. Irving, Kevin A. Janes, Michael J. Guertin, Kevin M. Weeks, Anindya Dutta

Cell Reports  ·  01 Feb 2022  ·  doi:10.1016/j.celrep.2022.110361

2021

Noncoding RNAs: biology and applications—a Keystone Symposia report

Jennifer Cable, Edith Heard, Tetsuro Hirose, Kannanganattu V. Prasanth, Ling‐Ling Chen, …, Mukesh Kumar Lalwani, Murat Can Kalem, Edward B. Chuong, Lynne E. Maquat, Xuhang Liu

Annals of the New York Academy of Sciences  ·  17 Nov 2021  ·  doi:10.1111/nyas.14713

Essentiality and Functional Importance of Short and Long Non-coding RNAs in Myogenesis

Roza Przanowska

University of Virginia  ·  25 Jun 2021  ·  doi:10.18130/frkw-fd05

2020

Oncogenic TRIM37 Links Chemoresistance and Metastatic Fate in Triple-Negative Breast Cancer

Piotr Przanowski, Song Lou, Rachisan Djiake Tihagam, Tanmoy Mondal, Caroline Conlan, …, Marty W. Mayo, Luis Teixeira, Jacqueline Lehmann-Che, Jogender Tushir-Singh, Sanchita Bhatnagar

Cancer Research  ·  01 Nov 2020  ·  doi:10.1158/0008-5472.can-20-1459

Tumour-derived CSF2/granulocyte macrophage colony stimulating factor controls myeloid cell accumulation and progression of gliomas

Malgorzata Sielska, Piotr Przanowski, Maria Pasierbińska, Kamil Wojnicki, Katarzyna Poleszak, …, Dominika Grzeganek, Aleksandra Ellert-Miklaszewska, Min-Chi Ku, Helmut Kettenmann, Bozena Kaminska

British Journal of Cancer  ·  11 May 2020  ·  doi:10.1038/s41416-020-0862-2

miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

Roza K. Przanowska, Ewelina Sobierajska, Zhangli Su, Kate Jensen, Piotr Przanowski, …, Jennifer A. Kashatus, David F. Kashatus, Sanchita Bhatnagar, John R. Lukens, Anindya Dutta

The FASEB Journal  ·  11 Apr 2020  ·  doi:10.1096/fj.201902855rr

miR‐206 family is important for mitochondrial and muscle function, but not essential for myogenesis in vitro

Roza K. Przanowska, Ewelina Sobierajska, Zhangli Su, Kate Jensen, Piotr Przanowski, …, Jennifer A. Kashatus, David F. Kashatus, Sanchita Bhatnagar, John R. Lukens, Anindya Dutta

The FASEB Journal  ·  11 Apr 2020  ·  doi:10.1096/fj.201902855RR

The pan-cancer landscape of prognostic germline variants in 10,582 patients

Ajay Chatrath, Roza Przanowska, Shashi Kiran, Zhangli Su, Shekhar Saha, …, Xiwei Tang, Tianxi Li, Pankaj Kumar, Aakrosh Ratan, Anindya Dutta

Genome Medicine  ·  17 Feb 2020  ·  doi:10.1186/s13073-020-0718-7

tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model

Zhangli Su, Elizabeth L. Frost, Catherine R. Lammert, Roza K. Przanowska, John R. Lukens, Anindya Dutta

RNA Biology  ·  31 Jan 2020  ·  doi:10.1080/15476286.2020.1721047

2019

Open chromatin landscape of rat microglia upon proinvasive or inflammatory polarization

Piotr Przanowski, Shamba S. Mondal, Aleksandra Cabaj, Konrad J. Dębski, Bartosz Wojtas, Bartłomiej Gielniewski, Beata Kaza, Bozena Kaminska, Michal Dabrowski

Glia  ·  24 Jul 2019  ·  doi:10.1002/glia.23686

A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome

Piotr Przanowski, Zeming Zheng, Urszula Wasko, Sanchita Bhatnagar

Journal of Visualized Experiments  ·  22 May 2019  ·  doi:10.3791/59449

Knockdown of STAT3 targets a subpopulation of invasive melanoma stem‐like cells

Dorota W Kulesza, Piotr Przanowski, Bozena Kaminska

Cell Biology International  ·  30 Apr 2019  ·  doi:10.1002/cbin.11134

2018

MUNC, an Enhancer RNA Upstream from the MYOD Gene, Induces a Subgroup of Myogenic Transcripts in trans Independently of MyoD

Magdalena A. Cichewicz, Manjari Kiran, Róża K. Przanowska, Ewelina Sobierajska, Yoshiyuki Shibata, Anindya Dutta

Molecular and Cellular Biology  ·  01 Oct 2018  ·  doi:10.1128/MCB.00655-17

A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective Strategy for Ovarian Cancer

Gururaj Shivange, Karol Urbanek, Piotr Przanowski, Justin S.A. Perry, James Jones, …, Marty Mayo, Kodi S. Ravichandran, Charles N. Landen, Sanchita Bhatnagar, Jogender Tushir-Singh

Cancer Cell  ·  01 Aug 2018  ·  doi:10.1016/j.ccell.2018.07.005

Pharmacological reactivation of inactive X-linked Mecp2 in cerebral cortical neurons of living mice

Piotr Przanowski, Urszula Wasko, Zeming Zheng, Jun Yu, Robyn Sherman, Lihua Julie Zhu, Michael J. McConnell, Jogender Tushir-Singh, Michael R. Green, Sanchita Bhatnagar

Proceedings of the National Academy of Sciences  ·  16 Jul 2018  ·  doi:10.1073/pnas.1803792115

Novel molecular players of X chromosome inactivation: new technologies and new insights

Piotr Przanowski, Urszula Waśko, Sanchita Bhatnagar

Journal of Translational Genetics and Genomics  ·  27 Feb 2018  ·  doi:10.20517/jtgg.2017.03

ISG'ylation increases stability of numerous proteins including Stat1, which prevents premature termination of immune response in LPS-stimulated microglia

Piotr Przanowski, Stefan Loska, Dominik Cysewski, Michal Dabrowski, Bozena Kaminska

Neurochemistry International  ·  01 Jan 2018  ·  doi:10.1016/j.neuint.2017.07.013

2017

Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment

D Mattei, A Ivanov, C Ferrai, P Jordan, D Guneykaya, …, B Kaminska, D Beule, A Pombo, H Kettenmann, S A Wolf

Translational Psychiatry  ·  09 May 2017  ·  doi:10.1038/tp.2017.80

2016

BIX01294, an inhibitor of histone methyltransferase, induces autophagy-dependent differentiation of glioma stem-like cells

Iwona Anna Ciechomska, Piotr Przanowski, Judyta Jackl, Bartosz Wojtas, Bozena Kaminska

Scientific Reports  ·  09 Dec 2016  ·  doi:10.1038/srep38723

Tumour-processed osteopontin and lactadherin drive the protumorigenic reprogramming of microglia and glioma progression

A Ellert-Miklaszewska, P Wisniewski, M Kijewska, P Gajdanowicz, D Pszczolkowska, P Przanowski, M Dabrowski, M Maleszewska, B Kaminska

Oncogene  ·  04 Apr 2016  ·  doi:10.1038/onc.2016.55

2015

Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma

Jakub Mieczkowski, Marta Kocyk, Pawel Nauman, Konrad Gabrusiewicz, Małgorzata Sielska, …, Wieslawa Grajkowska, Katarzyna Kotulska, Marcin Roszkowski, Boguslaw Kostkiewicz, Bozena Kaminska

Oncotarget  ·  29 Sep 2015  ·  doi:10.18632/oncotarget.5310

2014

Integration of genome-wide of Stat3 binding and epigenetic modification mapping with transcriptome reveals novel Stat3 target genes in glioma cells

Marcin Kruczyk, Piotr Przanowski, Michal Dabrowski, Karolina Swiatek-Machado, Jakub Mieczkowski, …, Anna Ronowicz, Arkadiusz Piotrowski, Claes Wadelius, Bozena Kaminska, Jan Komorowski

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms  ·  01 Nov 2014  ·  doi:10.1016/j.bbagrm.2014.07.010

2013

The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia

Piotr Przanowski, Michal Dabrowski, Aleksandra Ellert-Miklaszewska, Michal Kloss, Jakub Mieczkowski, …, Feng Hu, Arkadiusz Piotrowski, Helmut Kettenmann, Jan Komorowski, Bozena Kaminska

Journal of Molecular Medicine  ·  06 Oct 2013  ·  doi:10.1007/s00109-013-1090-5

Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response

Malgorzata Sielska, Piotr Przanowski, Bartosz Wylot, Konrad Gabrusiewicz, Marta Maleszewska, …, Katyayni Vinnakota, Helmut Kettenmann, Katarzyna Kotulska, Wieslawa Grajkowska, Bozena Kaminska

The Journal of Pathology  ·  07 Jun 2013  ·  doi:10.1002/path.4192

2011

Blocking Hypoxia-Induced Autophagy in Tumors Restores Cytotoxic T-Cell Activity and Promotes Regression

Muhammad Zaeem Noman, Bassam Janji, Bozena Kaminska, Kris Van Moer, Sandrine Pierson, …, Stéphanie Buart, Guy Berchem, Pedro Romero, Fathia Mami-Chouaib, Salem Chouaib

Cancer Research  ·  13 Sep 2011  ·  doi:10.1158/0008-5472.can-11-1094