- In German: unsere-wissenschaft-für-die-Öffentlichkeit
- In French: notre-science-pour-le-public
- In Italian: la-nostra-scienza-al-pubblico
Breast cancer is the second leading cause of cancer death in women and 2.1 million new patients are diagnosed with breast cancer annually. While 98% of patients survive 5 years or more after diagnosis of a localized (confined to the primary site) breast cancer, this number drops to 15-25% if the cancer has metastasized to distant organs. Thus, curing metastatic breast cancer is clearly an unmet medical need. The cellular and biochemical mechanisms that lead to drug-resistant metastases remain largely unknown and their identification has been the focus of the Bentires-Alj lab for the last 20 years. New therapies are likely to result from a more thorough understanding of cancer as a systemic disease involving both genomic alteration of cancer cells and dynamic crosstalk between cancer cells and the tumor microenvironment (e.g., immune cells). Our goal is to better understand breast cancer so as to better treat it.
- AACR Outstanding Investigator Award for breast cancer research 2015 – American Association for Cancer Research (EN)
“If I have seen further it is by standing on the shoulders of Giants”, wrote Isaac Newton.
Observation and research in mammary gland biology and cancer over the previous centuries have laid the foundation for our current understanding of this fascinating organ. But, despite the spectacular breakthroughs in our understanding of its pathophysiology and the corresponding clinical advances made by several key figures in our field (for an oral history of our field, see ENBDC / Interviews), breast cancer is still a source of worry and distress for patients.
Our lab consists of four subgroups. These interdisciplinary projects seek to leverage a mechanistic insight into personalized therapy, which is a recent focus of the translational research that we pursue in close collaboration with clinicians from the University Hospital Basel (USB) (www.bentireslab.org). In this page, we summarize our basic and translational research goals and some of our findings, and highlight our efforts in personalized medicine in Basel, in Switzerland, and worldwide.
Normal and neoplastic breast stem cells
Breast cancer is a heterogeneous disease and, besides the nature and number of genomic-transforming events and microenvironmental factors, the differentiation state of the cell-of-origin of cancer also determines the phenotype, tumorigenicity, and metastatic potential of this malignancy. This subgroup assesses fundamental mechanisms that influence normal and neoplastic breast stem cells.
- Reply to: Hippo signalling maintains ER expression and ER+ breast cancer growth.
Britschgi A, Couto JP, Bentires-Alj M. Nature. 2021 Mar;591(7848):E11-E12. doi: 10.1038/s41586-020-03132-4.
- The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERa.
Britschgi A, Duss S, Kim S, Couto JP, Brinkhaus H, Koren S, De Silva D, Mertz KD, Kaup D, Varga Z, Voshol H, Vissieres A, Leroy C, Roloff T, Stadler MB, Scheel CH, Miraglia LJ, Orth AP, Bonamy GM, Reddy VA, Bentires-Alj M. Nature. 2017 Jan 26;541(7638):541-545. doi: 10.1038/nature20829. Epub 2017 Jan 9.
- PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours.Koren S, Reavie L, Couto JP, De Silva D, Stadler MB, Roloff T, Britschgi A, Eichlisberger T, Kohler H, Aina O, Cardiff RD, Bentires-Alj M.
Nature. 2015 Sep 3;525(7567):114-8. doi: 10.1038/nature14669. Epub 2015 Aug 12.
- Common breast cancer mutation induces multipotency and tumor heterogeneity Press Release, FMI, 2015
- Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.
Meier-Abt F, Bentires-Alj M, Rochlitz C. Cancer Res. 2015 Mar 1;75(5):803-7. doi: 10.1158/0008-5472.CAN-14-2717. Epub 2015 Feb 6.
Cell Autonomous Mechanisms of Resistance & Metastasis
This subgroup focuses on cancer cells, studying how genetic/epigenetic alterations make cells harmful by forming a tumour and metastasizing to distant organs. We also study how breast cancer cells become resistant to therapy.
- New point of attack for breast cancer with poor prognosis, Media release, FMI, 2012
- Combination therapy for incurable metastatic breast cancer to circumvent therapy resistance, Media Release, FMI, 2012
- A team of researchers led by Momo Bentires-Alj discovered how stress hormones promote breast cancer metastasis
- The NFIB/ERO1A axis promotes breast cancer metastatic colonization of disseminated tumour cells
Zilli et al, EMBO Molecular Medicine https://www.embopress.org/doi/full/10.15252/emmm.202013162
Non-cell Autonomous mechanisms of resistance and metastasis
We study the effect of the immune system on breast cancer. Our work focuses on understanding the changes of the host immunity during disease progression and on how to harness the immune system to improve anticancer therapy.
- Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis.
Bonapace L, Coissieux MM, Wyckoff J, Mertz KD, Varga Z, Junt T, Bentires-Alj M.
Nature. 2014 Nov 6;515(7525):130-3. doi: 10.1038/nature13862. Epub 2014 Oct 22.
- Stopping anti-CCL2 breast cancer treatment aggravates the disease, Media release, FMI, 2014
“I have been impressed with the urgency of doing. Knowing is not enough; we must apply. Being willing is not enough; we must do.” (Leonardo da Vinci).
The Swiss Personalized Oncology (SPO):
The Swiss Personalized Oncology (SPO) driver project, part of the Swiss Personalized Health Network (SPHN), is chaired by Prof. M. Bentires-Alj and Prof. O. Michielin (CHUV, Lausanne). SPO is a Switzerland-wide effort that aims at integrating clinical and molecular information from cancer patients, which should ultimately enable more precise diagnoses and thus treatments tailored to individual patients. SPO’s main goal is to achieve interoperability of the clinical and laboratory data from cancer patients in Switzerland (www.unibas.ch/phb/oncology).
Personalized breast cancer treatment:
While the SPO is a nationwide effort, we have founded, together with Prof. Walter Weber (USB), the Basel Breast Consortium (https://baselbc.org), an interdisciplinary organization committed to the development of basic, clinical and translational research projects by supporting interdisciplinary communication and mutual education in Switzerland and neighbouring cities. We have also assembled, a local group of USB colleagues (Surgery, Gynecology, Pathology, Radiology, and Oncology) to make up a breast cancer personalized medicine team that should ultimately improve treatment of patients. Our goal is to collect patient samples and to use multiomics, combined with drug response profiling and computational analysis, in the assessment and modeling of cancer and tumor microenvironment heterogeneity in a longitudinal way. We apply a personalized systems medicine interdisciplinary approach to discover predictive biomarkers and mechanisms of resistance, to identify novel targets, and to rationally design combination therapy.
- Two projects led by consortia around DBM research group leaders Adrian Egli and Mohamed Bentires-Alj will receive federal support by the Swiss Personalised Health Network (SPHN)
- Patient-derived xenograft (PDX) models in basic and translational breast cancer research. Dobrolecki LE, Airhart SD, Alferez DG, Aparicio S, Behbod F, Bentires-Alj M, Brisken C, Bult CJ, Cai S, Clarke RB, Dowst H, Ellis MJ, Gonzalez-Suarez E, Iggo RD, Kabos P, Li S, Lindeman GJ, Marangoni E, McCoy A, Meric-Bernstam F, Piwnica-Worms H, Poupon MF, Reis-Filho J, Sartorius CA, Scabia V, Sflomos G, Tu Y, Vaillant F, Visvader JE, Welm A, Wicha MS, Lewis MT. Cancer Metastasis Rev. 2016 Dec;35(4):547-573. doi: 10.1007/s10555-016-9653-x.
Cancer poses a global challenge that requires global efforts:
Together with several colleagues, Prof. Bentires-Alj has created an international network of labs working on breast biology and cancer (www.enbdc.org) with the goal to foster scientific exchange and collaboration, as well as mutual training and education worldwide.
To develop more fidelitous ex vivo and in vivo models for studying breast cancer, we have teamed up with several labs to harmonize our respective collections of patient-derived organoids (PDOs) and primary-derived xenografts (PDXs). By combining efforts locally, nationally and internationally, we aim to create synergies that will lead to a better understanding of breast cancer biology and thus more relevant treatments.
Didn’t Aristotle say that “The whole is greater than the sum of its parts”?
Thank you to the different funding agencies and institutions who have supported our research so far and to colleagues and mentors for their great support. There are too many to be listed here but they will recognize themselves. It really takes a village to make discoveries: our lab members, past and current, who have been a source of daily joy in this â€œpleasure of finding things outâ€, the indispensable core facilities, and the administrative personnel who support our research. We are grateful to our friends and family for enriching our lives. As Albert Einstein said “Many times a day I realize how much my own outer and inner life is built upon the labors of my fellow human beings, both living and dead, and how earnestly I must exert myself in order to give in return as much as I have received”.
Research in the Bentires-Alj laboratory is supported by the Swiss Initiative for Systems Biology- SystemsX, the European Research Council (ERC advanced grant 694033 STEM-BCPC), the Swiss National Science Foundation, Novartis, the Krebsliga Beider Basel, the Swiss Cancer League, the Swiss Personalized Health Network (Swiss Personalized Oncology driver project), the Department of Biomedicine, the University of Basel, the University Hospital Basel, and the Department of Surgery of the University Hospital Basel.
Information about breast cancer and research:
- Swiss Cancer League (DE/FR/IT)
- Basel Krebs Liga (DE)
- Europa Donna (DE/FR/IT)
- American Association for Cancer Research – Breast Cancer
- National Health Service – Breast Cancer
- Cancer Research UK – Breast Cancer
- National Breast Cancer Foundation
- Cancer.gov – Breast Cancer
- e-cancer – Breast Cancer (FR)
- cancer.ca – Breast Cancer (FR)