Modelos murinos para el estudio de cáncer de mama triple negativo

Cauna-Orocollo, Yudith; Córdova-Salazar, Ariana Alessandra; Campos-Tineo, Jhanina; Cauna-Orocollo, Yudith; Córdova-Salazar, Ariana Alessandra; Campos-Tineo, Jhanina

doi:10.25176/rfmh.v23i4.6206

Serviços Personalizados

Journal

Artigo

Indicadores

Citado por SciELO

Links relacionados

Similares em SciELO

Mais
Mais

Permalink

Revista de la Facultad de Medicina Humana

versão impressa ISSN 1814-5469versão On-line ISSN 2308-0531

Rev. Fac. Med. Hum. vol.23 no.4 Lima out./dez. 2023 Epub 30-Nov-2023

http://dx.doi.org/10.25176/rfmh.v23i4.6206

Review article

Murine models for the study of triple negative breast cancer

Yudith Cauna Orocollo¹, Magister en Bioquímica y Biología Molecular

Ariana Alessandra Córdova Salazar¹, Bachiller en Biología

Jhanina Campos Tineo¹, Magister en Bioquímica y Biología Molecular

^¹Instituto de Investigaciones en Ciencias Biomédicas, Universidad Ricardo Palma. Lima, Perú

ABSTRACT

The study of different variables, such as pathogenesis, inflammatory profile, identification of therapeutic targets, efficacy of treatments in murine models has proven to be one of the most practical for the preclinical study of triple negative breast cancer (TNBC), the most aggressive subtype of cancer, with limited application of treatments and low survival rate. However, it must be recognized that there are other minors in which the induction of TNBC is being standardized. This review encompasses the different induction methods that have allowed the development of TNBC and the most relevant therapeutic applications by which murine models with TNBC were developed.

Keywords: murine model; triple negative breast cancer; induction; antitumor therapy. (Source: MESH-NLM)

INTRODUCTION

Breast cancer is the second most common malignant neoplasia in women, with high global incidence and mortality rates¹, and it could exceed 4.4 million patients by the year 2070². According to molecular classification, breast cancer is divided into subtypes based on the expression levels of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2). The molecular subtypes of breast cancer are luminal A (ER+ / PR+ / HER2-), luminal B (ER+ / PR+ / HER2+), HER2+ (ER- / PR- / HER2+), and triple-negative (ER- / PR- / HER2-), the latter having a worse prognosis compared to other subtypes³. Additionally, it is divided into basal-like and normal-like subtypes, the difference between these two subtypes lies in the expression of CK5, being CK5+ and CK5-, respectively⁴.

To accelerate the discovery of therapeutic targets for prospective treatments and breast cancer prevention, animal models are required for preclinical studies⁵. Immunocompromised murine models with triple-negative breast cancer (TNBC) have been developed⁴^,⁵, such as BALB/c strain mice and Sprague-Dawley strain rats, which have allowed the evaluation of pharmacokinetics, pathogenesis, inflammatory profile, microbiome, gene expression levels, and determination of effective doses, toxicity of chemical compounds, etc.⁶^,⁹. The objective of this review is to summarize the methods of TNBC induction in murine models, the therapeutic applications evaluated to date, and their advantages and disadvantages for the study of TNBC.

SEARCH STRATEGY

The search strategy for the bibliographic references of this review was meticulously structured, using a combination of keywords and Boolean operators to refine the results. The keywords used in English were: 'triple negative breast cancer', 'murine model', 'rat model', 'cell', 'xenograft', 'allograft', 'chemical cancer inductor', 'ionizing radiation', 'radiotherapy', 'chemotherapy', 'immunotherapy', and 'probiotics', related to 'animal model breast cancer'. These were combined using Boolean operators such as 'AND' and 'OR' to optimize the search. The search was conducted on search engines like PubMed, Google Scholar, and Science Direct. In addition, stringent selection criteria were established for the articles, prioritizing recent studies with high impact and relevance to the topic, thus ensuring that the review was based on the most current and pertinent literature.

METHODS AND DEVELOPMENT OF MURINE MODELS WITH TNBC

There are chemical, physical, and biological methods that promote carcinogenesis and are administered by different routes.

Among the biological induction methods for the development of breast cancer, the transplantation of grafts, cell lines, and tissues from murine models or women with breast cancer was significant in studying the pathogenesis of one of the breast cancer subtypes for the development of personalized therapies. The types of grafts are allografts or homografts, which involve using tissues or cells from one animal and transplanting them into another animal of the same species (Figure 1A), and xenografts or heterografts, which are obtained from humans and transplanted into an animal (Figure 1B, 1C)⁹. Although there are two types of grafts, the transplantation of xenografts is of greater importance for preclinical studies, as they involve human grafts.

The success of developing a murine model with breast cancer generally depends on the immunodeficiency of the animal for oncological studies, as the wild type immune response can be an obstacle to tumor growth and metastasis¹⁰. However, the applications of the study, such as the therapeutic composition intended for evaluation, must also be considered¹¹. Recently, the Sprague Dawley Rag2/Il2rg double-knockout (SRG OncoRat) immunosuppressed model for oncology studies was developed and validated. It showed a reduction in the tissue volume of the spleen and thymus, and consequently, a decrease in circulating T, NK, and B cells (Figure 2)⁷.

Biological Induction of TNBC

Transgenic Murine Models Mediated by Viruses

The use of foreign DNA has allowed the development of transgenic murine models for the induction of breast cancer. Lentiviruses promote the overexpression of oncogenes, specifically HER2/ERBB2, PyMT, Wnt, Myc, Ras, and PIK3CA, or the suppression of the expression of these genes in transgenic murine models⁹. Mice transgenic for Wnt-1 with extensive ductal hyperplasia is also a murine model for studying the pathology of TNBC¹².

Compared to other methods of breast cancer induction, this method includes high rates of incidence, short latencies, and more reliable results; the disadvantages are long incubation periods, varying times of incidence, and heterogeneous pathological characteristics⁹.

Murine Models with Breast Cancer Knockout in Tumor Suppressor Genes

These models were developed by knocking out tumor suppressor genes p53, BRCA1/2, and pTEN in mice using recombinase systems, with 50% of the population susceptible to developing breast cancer¹³^,¹⁴. Other murine knockout models use inducible systems, such as Cre-loxP for the conditional expression of Brca1, or the Tet-off/Tet-on system for the conditional expression of human PIK3CA¨H1047R, to achieve a high incidence rate (95%) with signs of adenocarcinoma and primary tumor phenotypes over incubation periods of 7 months¹⁵^,¹⁶.

Orthotopic Induction Based on Xenografts Derived from TNBC Cell Lines

It is commonly reported that the orthotopic route for cell inoculation in mice is in the mammary fat pad¹⁷^,¹⁹. Other more complex orthotopic routes include the intraductal pathway⁹^,²⁰^,²¹, mammary nipple canal²², right or left flank²³^,²⁴, or heterotopic subdermal²⁵or subcutaneous routes²¹^,²⁶^,²⁷.

The 4T1 cell line is one of the most commonly used to induce TNBC in the allograft mouse model. Using this cell line, the metastatic TNBC model was developed in different FVB/N and BALB/c mice using the mammary intraductal method, which involves making a cut at the base of the nipple to access the main duct of the mammary glands and inoculating 5 x 10^4 cells in 5 µL²⁸. Additionally, there are other breast cancer cell lines from genetically modified mice that promote the development of luminal and basal breast cancer and also generate metastases to the lungs and other organs (Table 1)⁸.

Among other murine breast cancer cell lines, one study developed the murine model with TNBC by injecting 10^6 cells from the D2A1 line in 100 µL into the mammary gland, resulting in pulmonary metastasis²⁹. In another study, 5x10^4 cells in 20 µL of the murine JygMC(A) cell line, with a triple-negative phenotype, were inoculated into the inguinal pad of the mammary fat tissue of athymic mice, observing the early appearance of tumors³⁰.

Human cell lines isolated from patients with TNBC have also been employed for the development of murine xenograft models, considering the negative expression of ER, PR, and HER2, and the histopathological characteristics generated by each cell line (Table 2); moreover, they have been classified into two subtypes of TNBC, Triple-Negative A or basal-like (TNA) and Triple-Negative B or normal-like (TNB)³¹.

Among the mentioned human cell lines for the induction of TNBC, MDA-MB-231 stands out as one of the most used. In one study, 10^7 MDA-MB-231 cells in 100µl were subcutaneously inoculated into the right flank of nude mice, resulting in the formation of visible tumors in less than 15 days²³. Nofiele & Cheng employed the same cell line to induce TNBC in healthy 6-week-old immunodeficient female rats and determined that ultrasound is necessary for the appearance of primary tumors³².

In another study, non-obese diabetic immunodeficient (NOD/SCID) mice were used, into which 3 x 10^6 cells in 100µl were inoculated in the mammary fat pad, observing a slower initial growth of MDA-MB-231 tumors compared to 4T1 tumors²⁵.

Induction Based on Xenografts Derived from Breast Tissue with TNBC

The development of breast cancer in murine models from xenografts derived from breast tissues of patients with TNBC has been a significant challenge in terms of histocompatibility. For instance, nude mice with a mutation in the Foxn1nu gene, deficient in B lymphocyte development and with increased activity of NK lymphocytes, can tolerate xenografts derived from human cell lines, but not xenografts derived from human tissues³³.

Recently, a murine model of patient-derived xenograft (PDX) was developed from tumor aspirates, which were concentrated and orthotopically transplanted into immunodeficient mice. It was reported that out of 269 xenografts, 62 were successful³⁴, indicating a very low efficiency of this method for the development of murine models with TNBC.

Induction of TNBC by Chemical Compounds

Carcinogen induction is one of the most practical methods for the development of breast cancer in murine models. The carcinogens commonly used in murines include DMBA (7,12-dimethylbenz[a]anthracene), MCA (3-methylcholanthrene), 1,2,5,6 dibenz[a]anthracene, MNU (N-methyl-N-nitrosourea), 2-acetylamino-fluorene, 3,4-benzopyrene, ethylnitrosourea, and butylnitrosourea, which generate B-type adenomas and adenocarcinomas⁹^,³⁵^,³⁶. DMBA and MNU, which are hormone-dependent, induce breast cancer in rats with ER-alpha-positive type.

On the other hand, ACI, Sprague Dawley, Fisher 344, Inbred S-D rats administered with 17 β-estradiol overexpressed ER and PR, and binding protein 3 (Gata3), making them an ideal model for the study of luminal subtype breast cancer or hormone-dependent breast cancer⁹^,²¹^,³⁷^,³⁸. No information was found on carcinogens used specifically for the development of TNBC.

Induction of TNBC by Ionizing Radiation

There are few studies focused on the specific induction of TNBC by ionizing radiation (IR). The most commonly used type of IR were X-rays for the induction of breast cancer under a sublethal dose, 0.2 Gy, in Sprague Dawley rats and BALB/c mice³⁹. Other types of ionizing radiation (IR), such as 177Lu neutrinos and gamma rays, are also capable of inducing lymphopenia and tumorigenesis in murine models³⁹^,⁴⁰.

In another study, it was evidenced that mammary tumors in irradiated rats were primarily hormone-dependent adenocarcinomas and fibroadenomas. However, in 2020, X-rays were used on MDA-MB-231 cells to generate a TNBC xenograft model with characteristics of radioresistance⁴¹.

THERAPEUTIC APPLICATIONS IN MURINE MODELS WITH TNBC

Chemotherapy in Murine Models with TNBC

Chemotherapy is the primary systemic treatment against early or advanced TNBC, however, the cellular heterogeneity found in TNBC patients promoted resistance to this type of therapy⁴².

Previously, GEMM mice (BRCA1 mutant breast cancer mice) (BRCA1Co/Co - MMTV-Cre-p53+/− mice) were used to evaluate Cisplatin against TNBC, individually or combined with OMO-1, a selective inhibitor of the epithelial-mesenchymal transition factor (c-MET), which reduced tumor progression²²^,⁴³. In another study, the action of Veliparib and Olaparib as ADP ribose polymerase (PARP) inhibitors was evaluated, and a delay in the development of BRCA1-deficient (TNBC) tumors was observed in a mouse model⁴⁴.

On the other hand, chemotherapy may require supplementary compounds to enhance the activity of drugs. In one study, the antitumor effect of doxorubicin/cyclosporine combined with IMMUNEPOTENT CRP, an immunomodulator comprising a mixture of small molecules derived from bovine spleen, was observed in an allograft murine model with TNBC⁴⁵. Other chemotherapy regimens act synergistically with immunotherapy. This is the case with α5β1 integrin-marked paclitaxel micellar (ATN-MPTX), ATN protein deposited in micelles, plus nano-STING, an activator of the innate immune pathway STING, resulting in reduced tumor volume and mitigated lung metastasis⁴⁶.

Radiotherapy in Murine Models with TNBC

Radiotherapy is a form of treatment based on the use of X-rays or gamma rays to halt cancer development, following criteria of effective dose, exposure time, and localized or complete administration⁴⁷.

Hormonal therapies are not useful for TNBC, hence radiotherapy is one of the treatment options against TNBC⁴⁰^,⁴⁸. Various studies have demonstrated its efficacy in reducing the likelihood of locoregional recurrence and increasing patient survival rates. However, these are insufficient, added to the resistance and side effects caused by high doses of IR⁴⁷^,⁴⁹.

In recent years, new radio sensitization targets have been identified, such as alkylphosphocholines overexpressed in malignant cells. Its analogue is 18-(p-iodophenyl) octadecyl phosphocholine, which, when marked with the radioisotope 125I, becomes CLR 125, a radiotherapy agent. It was administered in murine models with subcutaneous and metastatic TNBC xenografts, resulting in the destruction of cancer cells⁵⁰.

In one study, the effectiveness of tumor cell destruction based on proton therapy in mice with MDA-MB-231 xenografts was reported⁵¹. In the same group of novel therapies is photobiomodulation (PBM), which, in combination with radiotherapy in BALB/c allograft mice, showed that PBM retained tumor growth, attenuated the negative effects of radiotherapy, and halted metastasis⁴⁷. Another radiosensitization method evaluated in allograft mice was based on the use of D-mannose, a sugar that destabilizes the mRNA of BRCA1, RAD50, and MRE11, which inhibited tumor growth⁴⁸. Likewise, radiochemotherapy based on 177Lu-NM600, evaluated in an allograft murine model, was effective against TNBC, increasing survival time⁴⁰.

Immunotherapy in Murine Models with TNBC

Generally, immunotherapy is based on the use of antigens identified in tumor cells to generate a tumoricidal effect and suppress the production of immunosuppressive molecules, addressing resistance to chemotherapy⁸^,⁴².

One of the immunotherapy methods against TNBC in a heterotopic murine model was the administration of antibodies against aspartic protease cathepsin D (cath-D), overexpressed in breast cancer tumor cells, which inhibited tumor growth and promoted the activation of NK cells and inactivation of M2 macrophages⁵². However, the tumor infiltrate also consists of a heterogeneous immune profile that generates immunotherapeutic resistance³⁶^,⁵³. There are 2 immune subtypes of TNBC, the neutrophil-enriched immunosuppressive subtype (NES), and the macrophage-enriched subtype (MES), both resistant to immune blockade⁵³.

Due to immune heterogeneity, vaccines based on tumor membrane vesicles from the 4T1 cell line (TMV vaccine) combined with anti-CTLA-4 antibodies have been developed, promoting the activation of T lymphocytes against TNBC in allograft murine models⁵⁴. On the other hand, an immunotherapeutic method with high tumoricidal activity based on granulocyte-macrophage colony-stimulating factor (GM-CSF) was developed in an allograft mouse model⁽⁵⁵⁾. Xu et al. developed puerarin in nanoemulsion, named nanoPue, which, when administered in murine models with TNBC, reduced the activity of tumor-associated fibroblasts and increased the infiltration of cytotoxic T lymphocytes and M1 macrophages⁵⁶.

Probiotic-Based Therapy in Murine Models with TNBC

Due to the high rate of resistance to the aforementioned therapies, alternative complementary approaches effective against TNBC have also been evaluated. In recent years, the importance of probiotics, strains of microorganisms with anti-inflammatory, immunomodulatory, antimetastatic, and antiangiogenic properties, has been recognized, as the gastrointestinal microbiota regulates the adaptive immune system, and its alteration can lead to immunosuppression and increased susceptibility to cancer.

For instance, it was demonstrated that the oral administration of Lactobacillus acidophilus, Lactobacillus plantarum encapsulated in selenium nanoparticles, Lactobacillus helveticus R389, Bifidobacterium longum RAPO combined with anti-PD-1 antibodies, and fermented milk with Lactobacillus casei CRL 431 reduced tumor growth and metastasis, favored the infiltration of CD4+ and CD8+ lymphocytes, and induced apoptosis of tumor cells in the 4T1 allograft murine model⁵⁸^,⁶⁰^,⁶². Similarly, the oral administration of Bifidobacterium bifidum in the same model reduced the expression of Ki67, a protein associated with cell proliferation, and increased the expression of p53, a tumor suppressor protein⁶³.

ADVANTAGES AND DISADVANTAGES OF USING MURINE MODELS WITH TNBC

BALB/c mice are the most commonly used murine models in TNBC research studies⁹^,¹⁸^,³²^,⁶⁴, with NSG (NOD/SCID/γc−/−) mice being the most effective immunosuppressed models for the development of metastasis from breast cancer, compared to nude (athymic) mice (Puchalapalli et al., 2016). On the other hand, Sprague-Dawley rats, also known as Holtzman rats (Rattus norvegicus), have been less used but showed greater advantages due to their larger volume of tissue and fluid biopsies in contrast to NSG and SCID/NCr immunosuppressed mice (Figure 3), greater tumor growth, better capacity for non-invasive imaging, and easier surgical manipulation⁷.

One of the disadvantages of using murine models, whether mice or rats, is the demand for extensive vivarium areas and financial resources, as well as specialized human resources for handling these animals. Other less demanding animal models are being developed, smaller in size and more cost-effective, for example, the zebrafish model⁶⁵. In this model, it has been noted that the time for cancer development, depending on its stage, can be between 5 to 7 days (larval stage) or weeks to months (immunosuppressed adult stage), as in mice, but using a larger number of cells (10^5 - 10^6 cells) than in zebrafish⁶⁵. However, the size of biopsies for histopathology remains a benefit for the use of murine models, even more so in rats⁷.

CONCLUSIONS

Thus, animal models, particularly murine models, are relevant in the study of TNBC. The methods developed for the induction of TNBC, using cell lines for allograft models (e.g., mouse 4T1 cell line) and xenograft models (e.g., human MDA-MB-231 cell line), with prior immunosuppression of the animal, have been successfully developed for the evaluation of the pathology and the proposal of therapies against TNBC. As previously reported, TNBC has not been successfully induced by chemical compounds, and there are very few studies reporting the induction of TNBC by ionizing radiation.

Among the therapeutic applications evaluated in murine models with TNBC, innovative treatments have been proposed to address the high rate of resistance to chemotherapy, mediated by ionizing radiation, immunotherapy, and probiotic consumption, with the regulation of the microbiome being a complementary mechanism to achieve a greater antitumor effect.

REFERENCES

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. mayo de 2021;71(3):209-49. [ Links ]

2. Soerjomataram I, Bray F. Planning for tomorrow: global cancer incidence and the role of prevention 2020-2070. Nat Rev Clin Oncol. octubre de 2021;18(10):663-72. [ Links ]

3. Vidoni C, Vallino L, Ferraresi A, Secomandi E, Salwa A, Chinthakindi M, et al. Epigenetic control of autophagy in women's tumors: role of non-coding RNAs. J Cancer Metastasis Treat [Internet]. 1 de enero de 2021 [citado 28 de noviembre de 2023];2021. Disponible en: https://iris.uniupo.it/handle/11579/121513 [ Links ]

4. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 10 de agosto de 2014;5(3):412-24. [ Links ]

5. Singhal SS, Garg R, Mohanty A, Garg P, Ramisetty SK, Mirzapoiazova T, et al. Recent Advancement in Breast Cancer Research: Insights from Model Organisms-Mouse Models to Zebrafish. Cancers. enero de 2023;15(11):2961. [ Links ]

6. Gupta A, Jain GK, Raghubir R. A time course study for the development of an immunocompromised wound model, using hydrocortisone. J Pharmacol Toxicol Methods. agosto de 1999;41(4):183-7. [ Links ]

7. Noto FK, Sangodkar J, Adedeji BT, Moody S, McClain CB, Tong M, et al. The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies. PLOS ONE. 7 de octubre de 2020;15(10):e0240169. [ Links ]

8. Yang Y, Yang HH, Hu Y, Watson PH, Liu H, Geiger TR, et al. Immunocompetent mouse allograft models for development of therapies to target breast cancer metastasis. Oncotarget. 9 de mayo de 2017;8(19):30621-43. [ Links ]

9. Zeng L, Li W, Chen CS. Breast cancer animal models and applications. Zool Res. 18 de septiembre de 2020;41(5):477-94. [ Links ]

10. Puchalapalli M, Zeng X, Mu L, Anderson A, Glickman LH, Zhang M, et al. NSG Mice Provide a Better Spontaneous Model of Breast Cancer Metastasis than Athymic (Nude) Mice. PLOS ONE. 23 de septiembre de 2016;11(9):e0163521. [ Links ]

11. Korangath P, Barnett JD, Sharma A, Henderson ET, Stewart J, Yu SH, et al. Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer. Sci Adv. 2020;6(13). [ Links ]

12. Li Y, Hively WP, Varmus HE. Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breast cancer. Oncogene. 21 de febrero de 2000;19(8):1002-9. [ Links ]

13. Ding Q, Gan L. Conditional control of gene expression in the mouse retina. Methods Mol Biol Clifton NJ. 2012;884:3-15. [ Links ]

14. Stambolic V, Tsao MS, Macpherson D, Suzuki A, Chapman WB, Mak TW. High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice. Cancer Res. 1 de julio de 2000;60(13):3605-11. [ Links ]

15. Liu P, Cheng H, Santiago S, Raeder M, Zhang F, Isabella A, et al. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med. 7 de agosto de 2011;17(9):1116-20. [ Links ]

16. Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, et al. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet. mayo de 1999;22(1):37-43. [ Links ]

17. Arzi L, Farahi A, Jafarzadeh N, Riazi G, Sadeghizadeh M, Hoshyar R. Inhibitory Effect of Crocin on Metastasis of Triple-Negative Breast Cancer by Interfering with Wnt/ß-Catenin Pathway in Murine Model. DNA Cell Biol. diciembre de 2018;37(12):1068-75. [ Links ]

18. Kaur P, Nagaraja GM, Zheng H, Gizachew D, Galukande M, Krishnan S, et al. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease. BMC Cancer. 27 de marzo de 2012;12:120. [ Links ]

19. Zhang Q, Le K, Xu M, Zhou J, Xiao Y, Yang W, et al. Combined MEK inhibition and tumor-associated macrophages depletion suppresses tumor growth in a triple-negative breast cancer mouse model. Int Immunopharmacol. 1 de noviembre de 2019;76:105864. [ Links ]

20. Ahn RW, Chen F, Chen H, Stern ST, Clogston JD, Patri AK, et al. A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 15 de julio de 2010;16(14):3607-17. [ Links ]

21. Boix-Montesinos P, Soriano-Teruel PM, Armiñán A, Orzáez M, Vicent MJ. The past, present, and future of breast cancer models for nanomedicine development. Adv Drug Deliv Rev. 1 de junio de 2021;173:306-30. [ Links ]

22. Steenbrugge J, Breyne K, Demeyere K, De Wever O, Sanders NN, Van Den Broeck W, et al. Anti-inflammatory signaling by mammary tumor cells mediates prometastatic macrophage polarization in an innovative intraductal mouse model for triple-negative breast cancer. J Exp Clin Cancer Res. 15 de agosto de 2018;37(1):191. [ Links ]

23. García-Castillo V, López-Urrutia E, Villanueva-Sánchez O, Ávila-Rodríguez MÁ, Zentella-Dehesa A, Cortés-González C, et al. Targeting Metabolic Remodeling in Triple Negative Breast Cancer in a Murine Model. J Cancer. 13 de enero de 2017;8(2):178-89. [ Links ]

24. Malekian S, Rahmati M, Sari S, Kazemimanesh M, Kheirbakhsh R, Muhammadnejad A, et al. Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer. Adv Pharm Bull. junio de 2020;10(2):323-8. [ Links ]

25. Arroyo-Crespo JJ, Armiñán A, Charbonnier D, Deladriere C, Palomino-Schätzlein M, Lamas-Domingo R, et al. Characterization of triple-negative breast cancer preclinical models provides functional evidence of metastatic progression. Int J Cancer. 15 de octubre de 2019;145(8):2267-81. [ Links ]

26. Okano M, Oshi M, Butash A, Okano I, Saito K, Kawaguchi T, et al. Orthotopic Implantation Achieves Better Engraftment and Faster Growth Than Subcutaneous Implantation in Breast Cancer Patient-Derived Xenografts. J Mammary Gland Biol Neoplasia. marzo de 2020;25(1):27-36. [ Links ]

27. Zamberi NR, Abu N, Mohamed NE, Nordin N, Keong YS, Beh BK, et al. The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells. Integr Cancer Ther. diciembre de 2016;15(4):NP53-66. [ Links ]

28. Ghosh A, Sarkar S, Banerjee S, Behbod F, Tawfik O, McGregor D, et al. MIND model for triple-negative breast cancer in syngeneic mice for quick and sequential progression analysis of lung metastasis. PloS One. 2018;13(5):e0198143. [ Links ]

29. Bouchard G, Therriault H, Geha S, Bérubé-Lauzière Y, Bujold R, Saucier C, et al. Stimulation of triple negative breast cancer cell migration and metastases formation is prevented by chloroquine in a pre-irradiated mouse model. BMC Cancer. 10 de junio de 2016;16(1):361. [ Links ]

30. Peeney D, Jensen SM, Castro NP, Kumar S, Noonan S, Handler C, et al. TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer. Carcinogenesis. 14 de mayo de 2020;41(3):313-25. [ Links ]

31. Costa E, Ferreira-Gonçalves T, Chasqueira G, Cabrita AS, Figueiredo IV, Reis CP. Experimental Models as Refined Translational Tools for Breast Cancer Research. Sci Pharm. septiembre de 2020;88(3):32. [ Links ]

32. Nofiele JT, Cheng HLM. Establishment of a Lung Metastatic Breast Tumor Xenograft Model in Nude Rats. PLOS ONE. 16 de mayo de 2014;9(5):e97950. [ Links ]

33. Souto EP, Dobrolecki LE, Villanueva H, Sikora AG, Lewis MT. In Vivo Modeling of Human Breast Cancer Using Cell Line and Patient-Derived Xenografts. J Mammary Gland Biol Neoplasia. junio de 2022;27(2):211-30. [ Links ]

34. Echeverria GV, Cai S, Tu Y, Shao J, Powell E, Redwood AB, et al. Predictors of success in establishing orthotopic patient-derived xenograft models of triple negative breast cancer. Npj Breast Cancer. 10 de enero de 2023;9(1):1-9. [ Links ]

35. Kassayová M, Bobrov N, Strojný L, Orendáš P, Demečková V, Jendželovský R, et al. Anticancer and Immunomodulatory Effects of Lactobacillus plantarum LS/07, Inulin and Melatonin in NMU-induced Rat Model of Breast Cancer. Anticancer Res. junio de 2016;36(6):2719-28. [ Links ]

36. Liu Y, Hu Y, Xue J, Li J, Yi J, Bu J, et al. Advances in immunotherapy for triple-negative breast cancer. Mol Cancer. 2 de septiembre de 2023;22(1):145. [ Links ]

37. Shull JD, Dennison KL, Chack AC, Trentham-Dietz A. Rat models of 17ß-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention. Physiol Genomics. 1 de marzo de 2018;50(3):215-34. [ Links ]

38. Ruhlen RL, Willbrand DM, Besch-Williford CL, Ma L, Shull JD, Sauter ER. Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP-Ept2 rat model. Breast Cancer Res Treat. octubre de 2009;117(3):517-24. [ Links ]

39. Russo IH, Russo J. Mammary gland neoplasia in long-term rodent studies. Environ Health Perspect. septiembre de 1996;104(9):938-67. [ Links ]

40. Hernandez R, Grudzinski JJ, Aluicio-Sarduy E, Massey CF, Pinchuk AN, Bitton AN, et al. 177Lu-NM600 Targeted Radionuclide Therapy Extends Survival in Syngeneic Murine Models of Triple-Negative Breast Cancer. J Nucl Med. 1 de agosto de 2020;61(8):1187-94. [ Links ]

41. Zhou ZR, Wang XY, Yu XL, Mei X, Chen XX, Hu QC, et al. Building radiation-resistant model in triple-negative breast cancer to screen radioresistance-related molecular markers. Ann Transl Med. febrero de 2020;8(4):108. [ Links ]

42. Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. noviembre de 2016;13(11):674-90. [ Links ]

43. Shafee N, Smith CR, Wei S, Kim Y, Mills GB, Hortobagyi GN, et al. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res. 1 de mayo de 2008;68(9):3243-50. [ Links ]

44. To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res Phila Pa. julio de 2014;7(7):698-707. [ Links ]

45. Santana-Krímskaya SE, Franco-Molina MA, Zárate-Triviño DG, Prado-García H, Zapata-Benavides P, Torres-del-Muro F, et al. IMMUNEPOTENT CRP plus doxorubicin/cyclophosphamide chemotherapy remodel the tumor microenvironment in an air pouch triple-negative breast cancer murine model. Biomed Pharmacother. 1 de junio de 2020;126:110062. [ Links ]

46. Qiu X, Qu Y, Guo B, Zheng H, Meng F, Zhong Z. Micellar paclitaxel boosts ICD and chemo-immunotherapy of metastatic triple negative breast cancer. J Controlled Release. 1 de enero de 2022;341:498-510. [ Links ]

47. Silva CR, de Almeida Salvego C, Rostelato ME, Zeituni CA, Ribeiro MS. Photobiomodulation therapy combined with radiotherapy in the treatment of triple-negative breast cancer-bearing mice. J Photochem Photobiol B. 1 de julio de 2021;220:112215. [ Links ]

48. Zhang R, Yang Y, Dong W, Lin M, He J, Zhang X, et al. D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1. Proc Natl Acad Sci. 22 de febrero de 2022;119(8):e2114851119. [ Links ]

49. Anti-tumor responses to hypofractionated radiation in mice grafted with triple negative breast cancer is associated with decorin induction in peritumoral muscles. Acta Biochim Biophys Sin. 14 de agosto de 2018;1150-7. [ Links ]

50. Grudzinski J, Marsh I, Titz B, Jeffery J, Longino M, Kozak K, et al. CLR 125 Auger Electrons for the Targeted Radiotherapy of Triple-Negative Breast Cancer. Cancer Biother Radiopharm. abril de 2018;33(3):87-95. [ Links ]

51. Cammarata FP, Forte GI, Broggi G, Bravatà V, Minafra L, Pisciotta P, et al. Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams. Int J Mol Sci. enero de 2020;21(17):6337. [ Links ]

52. Ashraf Y, Mansouri H, Laurent-Matha V, Alcaraz LB, Roger P, Guiu S, et al. Immunotherapy of triple-negative breast cancer with cathepsin D-targeting antibodies. J Immunother Cancer. 4 de febrero de 2019;7(1):29. [ Links ]

53. Kim IS, Gao Y, Welte T, Wang H, Liu J, Janghorban M, et al. Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms. Nat Cell Biol. septiembre de 2019;21(9):1113-26. [ Links ]

54. Pack CD, Bommireddy R, Munoz LE, Patel JM, Bozeman EN, Dey P, et al. Tumor membrane-based vaccine immunotherapy in combination with anti-CTLA-4 antibody confers protection against immune checkpoint resistant murine triple-negative breast cancer. Hum Vaccines Immunother. 1 de diciembre de 2020;16(12):3184-93. [ Links ]

55. Liu X, Hu J, Cao W, Qu H, Wang Y, Ma Z, et al. Effects of two different immunotherapies on triple negative breast cancer in animal model. Cell Immunol. 1 de julio de 2013;284(1):111-8. [ Links ]

56. Xu H, Hu M, Liu M, An S, Guan K, Wang M, et al. Nano-puerarin regulates tumor microenvironment and facilitates chemo- and immunotherapy in murine triple negative breast cancer model. Biomaterials. 1 de marzo de 2020;235:119769. [ Links ]

57. De Almeida CV, de Camargo MR, Russo E, Amedei A. Role of diet and gut microbiota on colorectal cancer immunomodulation. World J Gastroenterol. 14 de enero de 2019;25(2):151-62. [ Links ]

58. Maroof H, Hassan ZM, Mobarez AM, Mohamadabadi MA. Lactobacillus acidophilus could modulate the immune response against breast cancer in murine model. J Clin Immunol. diciembre de 2012;32(6):1353-9. [ Links ]

59. Mendoza L. Potential effect of probiotics in the treatment of breast cancer. Oncol Rev. 27 de septiembre de 2019;13(2):422. [ Links ]

60. de Moreno de LeBlanc A, Matar C, LeBlanc N, Perdigón G. Effects of milk fermented by Lactobacillus helveticusR389 on a murine breast cancer model. Breast Cancer Res. 26 de abril de 2005;7(4):R477. [ Links ]

61. Kim H, Oh R, Heo JW, Ji GE, Park MS, Kim SE. Abstract LB532: Bifidobacterium longum RAPO alleviates the risk of immune-related adverse events of anti-PD-1 immunotherapy in a mouse model of triple-negative breast cancer. Cancer Res. 15 de junio de 2022;82(12_Supplement):LB532. [ Links ]

62. Yazdi MH, Mahdavi M, Kheradmand E, Shahverdi AR. The Preventive Oral Supplementation of a Selenium Nanoparticle-enriched Probiotic Increases the Immune Response and Lifespan of 4T1 Breast Cancer Bearing Mice. Arzneimittelforschung. noviembre de 2012;62(11):525-31. [ Links ]

63. Nazari F, Jafari P, Nomanpour B, Varmira K, Raissi F. Inhibitory effects of postbiotic consisting sonication-killed Bifidobacterium bifidum on experimental triple negative breast neoplasm in mice: a preliminary study. Iran J Microbiol. octubre de 2022;14(5):689-97. [ Links ]

64. Liu C, Wu P, Zhang A, Mao X. Advances in Rodent Models for Breast Cancer Formation, Progression, and Therapeutic Testing. Front Oncol [Internet]. 2021 [citado 12 de diciembre de 2023];11. Disponible en: https://www.frontiersin.org/articles/10.3389/fonc.2021.593337 [ Links ]

65. Fazio M, Ablain J, Chuan Y, Langenau DM, Zon LI. Zebrafish patient avatars in cancer biology and precision cancer therapy. Nat Rev Cancer. mayo de 2020;20(5):263-73. [ Links ]

Funding: Self-funded.

Article published by the Journal of the faculty of Human Medicine of the Ricardo Palma University. It is an open access article, distributed under the terms of the Creatvie Commons license: Creative Commons Attribution 4.0 International, CC BY 4.0 (https://creativecommons.org/licenses/by/1.0/), that allows non-commercial use, distribution and reproduction in any medium, provided that the original work is duly cited. For commercial use, please contact revista.medicina@urp.edu.pe.

Received: October 10, 2023; Accepted: December 20, 2023

Correspondence: Yudith Cauna - Orocollo. Address: Jr. Enrique Barreda 314, Lima - Perú. Phone: (+51) 949610400 E-mail:yudith.cauna@urp.edu.pe

Autorship contributions: The authors participated in the genesis of the idea, project design, data collection and interpretation, analysis of results and preparation of the manuscript of this research work.

Conflicts of interest: The authors declare that they have no conflict of interest.

Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons