scholarly journals Breast cancer dormancy: need for clinically relevant models to address current gaps in knowledge

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Grace G. Bushnell ◽  
Abhijeet P. Deshmukh ◽  
Petra den Hollander ◽  
Ming Luo ◽  
Rama Soundararajan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Late Relapse ◽  
The Past ◽  
Dormant Cells ◽  
Metastatic Relapse ◽  
Cancer Dormancy ◽  
Cellular Source ◽  
Estrogen Receptor Positive ◽  
The Usa

AbstractBreast cancer is the most commonly diagnosed cancer in the USA. Although advances in treatment over the past several decades have significantly improved the outlook for this disease, most women who are diagnosed with estrogen receptor positive disease remain at risk of metastatic relapse for the remainder of their life. The cellular source of late relapse in these patients is thought to be disseminated tumor cells that reactivate after a long period of dormancy. The biology of these dormant cells and their natural history over a patient’s lifetime is largely unclear. We posit that research on tumor dormancy has been significantly limited by the lack of clinically relevant models. This review will discuss existing dormancy models, gaps in biological understanding, and propose criteria for future models to enhance their clinical relevance.

scholarly journals Breast cancer dormancy is associated with a 4NG1 state and not senescence

2020 ◽  
Author(s):  
Chloé Prunier ◽  
Ania Alay ◽  
Michiel van Dijk ◽  
Kelly L. Ammerlaan ◽  
Sharon van Gelderen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell Line ◽  
Late Relapse ◽  
Future Research ◽  
Patient Death ◽  
Senescent Phenotype ◽  
Dormant Cells ◽  
Cancer Dormancy

ABSTRACTReactivation of dormant cancer cells can lead to cancer relapse, metastasis and patient death. Dormancy is a non-proliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and proliferative D2A1 breast cancer cell line models in vivo and in vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model. In vitro, we show that D2.OR cells are polyploid ER+/Her2+ cells, and in response to a 3D environment are growth arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible, and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.

scholarly journals Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy

2017 ◽  
Vol 24 (11) ◽  
pp. C21-C29 ◽  
Author(s):  
Giorgio Secreto ◽  
Paola Muti ◽  
Milena Sant ◽  
Elisabetta Meneghini ◽  
Vittorio Krogh
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Serum Testosterone ◽  
Late Relapse ◽  
Breast Cancer Patients ◽  
Estrogen Receptor Positive ◽  
Epidermal Growth

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptor-positive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials.

scholarly journals Breast cancer dormancy is associated with a 4NG1 state and not senescence

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chloé Prunier ◽  
Ania Alay ◽  
Michiel van Dijk ◽  
Kelly L. Ammerlaan ◽  
Sharon van Gelderen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell Line ◽  
Late Relapse ◽  
Future Research ◽  
Patient Death ◽  
Senescent Phenotype ◽  
Cancer Dormancy ◽  
Serum Free Conditions

AbstractReactivation of dormant cancer cells can lead to cancer relapse, metastasis, and patient death. Dormancy is a nonproliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and ZR-75-1, and proliferative D2A1 breast cancer cell line models in vivo and/or in vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model. In vitro, we show that D2.OR and ZR-75-1 cells in response to a 3D environment or serum-free conditions are growth-arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.

scholarly journals SLX4IP and telomere dynamics dictate breast cancer metastasis and therapeutic responsiveness

2020 ◽  
Vol 3 (4) ◽  
pp. e201900427
Author(s):  
Nathaniel J Robinson ◽  
Chevaun D Morrison-Smith ◽  
Alex J Gooding ◽  
Barbara J Schiemann ◽  
Mark W Jackson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Clinical Manifestations ◽  
Metastatic Breast ◽  
Disseminated Tumor Cells ◽  
Telomere Maintenance ◽  
Metastatic Progression ◽  
Metastatic Relapse

Metastasis is the leading cause of breast cancer-related death and poses a substantial clinical burden owing to a paucity of targeted treatment options. The clinical manifestations of metastasis occur years-to-decades after initial diagnosis and treatment because disseminated tumor cells readily evade detection and resist therapy, ultimately giving rise to recurrent disease. Using an unbiased genetic screen, we identified SLX4-interacting protein (SLX4IP) as a regulator of metastatic recurrence and established its relationship in governing telomere maintenance mechanisms (TMMs). Inactivation of SLX4IP suppressed alternative lengthening of telomeres (ALT), coinciding with activation of telomerase. Importantly, TMM selection dramatically influenced metastatic progression and survival of patients with genetically distinct breast cancer subtypes. Notably, pharmacologic and genetic modulation of TMMs elicited telomere-dependent cell death and prevented disease recurrence by disseminated tumor cells. This study illuminates SLX4IP as a potential predictive biomarker for breast cancer progression and metastatic relapse. SLX4IP expression correlates with TMM identity, which also carries prognostic value and informs treatment selection, thereby revealing new inroads into combating metastatic breast cancers.

Exploring New Targets and Publication Tendency of Triple Negative Breast Cancer: A 20-Year Bibliometric Analysis

2021 ◽  
Author(s):  
Xiaonan Sheng ◽  
Huijuan Dai ◽  
Yonggang Song ◽  
Xueyun Ma
Keyword(s):  
Breast Cancer ◽  
Bibliometric Analysis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Research Focus ◽  
The Past ◽  
The Usa

Abstract Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it lacks an efficient target treatment. Here, we aimed to gain knowledge on the development of TNBC research and explore potential treatment strategies.Methods: We analyzed 14,389 publications on TNBC from the Web of Science (WOS) over the past 20 years, from 2000 to 2020, using bibliometric methods. We evaluated the publication tendency of TNBC and the contributions of different countries. Institutions and journals with the highest number of TNBC publications were screened. Finally, the research focus of the TNBC publications were also analyzed.Results: TNBC publications have significantly increased in the past 20 years, with elevated relative research interest (RRI). The USA has the most TNBC-related publications with high quality, and China is the country with the most rapid growth tendency in TNBC publications. The University of Texas System is the institution with the most TNBC publications. Breast Cancer Research and Treatment is the journal that published the most TNBC-related publications. The top 30 publications with high citations are also listed. The researches focusing on TNBC in the past 20 years were separated into four main clusters: tumor biology, TNBC therapies, treatment sensitivity, and gene mutations. The research focus in TNBC ranked by appearing years reflects the development of TNBC treatment strategy, showing that targeting tumor immunity is now the main focus in TNBC research. Conclusions: Using bibliometric analysis, we initially revealed the increasing interest in TNBC research and summarized the publication tendency of TNBC. We also reported focused topics screened from publications in the past 20 years, indicating the main problems and research objectives of TNBC for the first time. Immune-related topics are becoming the focus of TNBC research.

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