Breast cancer remains the main cause of cancer-related mortality for women world-wide. Main cause of death is the development of therapy-resistant metastases. Relapses occur with a bimodal temporal distribution, with ...Breast cancer remains the main cause of cancer-related mortality for women world-wide. Main cause of death is the development of therapy-resistant metastases. Relapses occur with a bimodal temporal distribution, with a first peak at 1-2 years after initial therapy and a second peak 2-3 years later. This discontinuous growth kinetics is consistent with the notion that disseminated cancer cells can remain dormant over a prolonged period of time before resuming growth. How cancer cells enter, sustain and exit dormancy, are unanswered questions with relevance to cancer biology, monitoring and therapy. Investigating mechanisms of breast cancer dormancy remains challenging, as in patients the condition is elusive and experimentally there are only a few models that recapitulate the clinical condition. Thus, developing new models to identify clinically relevant mechanisms and candidate therapeutic targets may open new avenues for novel therapies to induce and prolong dormancy. We have observed that cells surviving chemotherapy can enter a state of immunological dormancy. Using this model, we identified IRF-7/Interferon type I/IFNRA as signaling axis essential for this effect. Here we will review concepts and recent developments in cancer metastasis and dormancy with emphasis on breast cancer, and elaborate strategies to exploit them therapeutically.展开更多
基金the Swiss National Sciences foundation(31003A_159824/1,31003A_179248/1)the Swiss Cancer League(KSF3513-08-2014,KSF-4400-02-2018)NCCR Molecular Oncology,NCCR Bio-Inspired materials,the Medic Foundation,the Sassella Stiftung,the 3R foundation,and the European Union under the auspices of the FP7 collaborative project TuMIC(HEALTH-F2-2008-201662)
文摘Breast cancer remains the main cause of cancer-related mortality for women world-wide. Main cause of death is the development of therapy-resistant metastases. Relapses occur with a bimodal temporal distribution, with a first peak at 1-2 years after initial therapy and a second peak 2-3 years later. This discontinuous growth kinetics is consistent with the notion that disseminated cancer cells can remain dormant over a prolonged period of time before resuming growth. How cancer cells enter, sustain and exit dormancy, are unanswered questions with relevance to cancer biology, monitoring and therapy. Investigating mechanisms of breast cancer dormancy remains challenging, as in patients the condition is elusive and experimentally there are only a few models that recapitulate the clinical condition. Thus, developing new models to identify clinically relevant mechanisms and candidate therapeutic targets may open new avenues for novel therapies to induce and prolong dormancy. We have observed that cells surviving chemotherapy can enter a state of immunological dormancy. Using this model, we identified IRF-7/Interferon type I/IFNRA as signaling axis essential for this effect. Here we will review concepts and recent developments in cancer metastasis and dormancy with emphasis on breast cancer, and elaborate strategies to exploit them therapeutically.
