Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

Aqbi, Hussein F.; Tyutyunyk‐Massey, Liliya; Keim, Rebecca; Butler, Savannah E.; Thekkudan, Theresa; Joshi, Supriya; Smith, Timothy M.; Bandyopadhyay, Dipankar; Idowu, Michael O.; Bear, Harry D.; Payne, Kyle K.; Gewirtz, David A.; Manjili, Masoud H.

doi:10.18632/oncotarget.25197

Cited by 53 publications

(47 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Complete medium was used to wash any remaining cells through the filter. Ki67 expression was determined as previously described by our group [ 20 , 21 ]. Cells were fixed with 70% ethanol and stained with anti-Ki67 for 30 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…However, they could be susceptible to immunotherapy if targeted before clinical recurrences [ 19 ]. Recently, we have reported that dormant tumor cells established by chemotherapy or radiation therapy became resistant to additional doses of these therapies but remained susceptible to immunotherapy [ 20 , 21 ]. Chemotherapy-induced immunogenic tumor dormancy maintained by the immune response has also been reported by others [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Although breast cancer mortality is a result of distant recurrences associated with the establishment of tumor dormancy, current clinical practice guidelines recommend a wait and watch approach for tumor recurrences. This is because of our limited understanding of tumor dormancy and insufficient evidence in support of immunological control of tumor dormancy. Methods We used FVBN202 transgenic mice expressing rat neu oncogene in the mammary glands, and their parental FVB strain lacking neu expression. These models allowed the detection of tumor dormancy at distant sites using the rat neu protein as a tumor marker. We also used Ki67 for the detection of the indolent and quiescent types of tumor dormancy. Multicolor flow cytometry was used to detect dormant tumor cells and T cell subsets. Co-culture studies were performed to determine the role of T cells in preventing regrowth of dormant cells. Results We demonstrated that dormant tumor cells were present at the site of primary breast cancer and at distant sites in the lungs and in the liver very early in the course of early stage breast cancer when no distant metastasis was evident. Dormant tumor cells were characterized as neu expressing Ki67− and Ki67low fractions associated with the induction of local immune responses predominated by CD4+ and CD8+ T effector cell subsets. The presence of neu-autoreactive T cells from FVBN202 mice only prevented regrowth of dormant cells. On the other hand, presence of neu-alloreactive anti-tumor T cells in FVB mice prior to tumor challenge resulted in the protection of mice from the dissemination of dormant tumor cells to distant organs. Conclusion Our results suggest that immunotherapeutic targeting of semi-allogeneic mutant neoantigens during tumor dormancy might prevent distant recurrence of the disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, results from a recent study showed the role of autophagy as an important regulator of metabolic tumor cell dormancy. That, the lack of autophagy, which is exploited as an important compensatory mechanism by tumor cells to provide their energy requirements, associates with an early breast cancer recurrence and escape from dormancy as demonstrated in neu-overexpressing mouse mammary carcinoma (MMC) [120].…”

Section: Metabolic Reprogrammingmentioning

confidence: 99%

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

Jahanban‐Esfahlan

Seidi

Manjili

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including angiogenic switch, immune escape, cancer stem cells, extracellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer and discuss the implications of such approaches in cancer treatment.

show abstract

“…Autophagy also promotes survival of DTC against chemotherapy-induced cell stress [126] . On the other side, in breast cancer the lack of autophagy is associated with early tumor recurrence and escape from dormancy [127] . It is important to note, that cellular dormancy is not just a feature of cancer cells but it also occurs in normal cells.…”

Section: Cellular Dormancy: Survival Of Non-proliferating Solitary Cellsmentioning

confidence: 99%

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

Peyvandi¹,

Lan²,

Lorusso³

et al. 2019

JCMT

View full text Add to dashboard Cite

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.

show abstract

Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy

Cited by 53 publications

References 31 publications

Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets

Local and distant tumor dormancy during early stage breast cancer are associated with the predominance of infiltrating T effector subsets

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

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

Contact Info

Product

Resources

About