Chemotherapy-induced immunological breast cancer dormancy: a new function for old drugs?

Abstract

Breast cancer remains the main cause of cancer-related mortality for women worldwide. 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.

Oligometastatic Breast Cancer: Is This a Curable Entity? A Contemporary Review of the Literature

“…At some later point, they exit dormancy and acquire further genetic changes that enable a more phenotypically plastic cell, thereby allowing it to resist hostile selective pressures at distant sites. Somewhere in this transit period, the cells presumably have not yet reached their full metastatic potential and can achieve metastasis in a select few sites that provide a more favorable niche [13].…”

Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer

“…ICD induces an adaptive immune response against tumor cells in an immunocompetent host [ 27 , 28 ]. Immune infiltrations, especially tumor-infiltrating lymphocytes (TILs), have a marked effect on the response of adjuvant and neoadjuvant chemotherapies and in determining the final clinical outcome [ 29 , 30 , 31 ]. The presence of TILs, particularly CD8 + T cells and tumor-infiltrating natural killer (NK) cells, correlate with an enhanced pathological complete response (PCR), a reduced risk of recurrence, and better survival in TNBC patients [ 32 , 33 ].…”

Switching Homes: How Cancer Moves to Bone

“…However, Abravanel and colleagues obtained different results when investigating the Notch family [181], likely because fine-tuning such an important pathway might cause dramatic differences, as is shown in other reports in the literature [176]. Another pathway that is still under investigation in this regard is the already cited SDF-1/CXCR4 pathway, which might partake in this process as well, although there is currently no consensus on the matter, and results seem to be pointing at different directions in different cancers [182][183][184][185].…”