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  1. Article: Emerging Targeted Therapies for HER2-Positive Breast Cancer.

    Mercogliano, María Florencia / Bruni, Sofía / Mauro, Florencia Luciana / Schillaci, Roxana

    Cancers

    2023  Volume 15, Issue 7

    Abstract: Breast cancer is the most common cancer in women and the leading cause of death. HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival. Tratuzumab, a monoclonal antibody ...

    Abstract Breast cancer is the most common cancer in women and the leading cause of death. HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival. Tratuzumab, a monoclonal antibody directed against the HER2 receptor, is the standard of care treatment. However, a third of the patients do not respond to therapy. Given the high rate of resistance, other HER2-targeted strategies have been developed, including monoclonal antibodies such as pertuzumab and margetuximab, trastuzumab-based antibody drug conjugates such as trastuzumab-emtansine (T-DM1) and trastuzumab-deruxtecan (T-DXd), and tyrosine kinase inhibitors like lapatinib and tucatinib, among others. Moreover, T-DXd has proven to be of use in the HER2-low subtype, which suggests that other HER2-targeted therapies could be successful in this recently defined new breast cancer subclassification. When patients progress to multiple strategies, there are several HER2-targeted therapies available; however, treatment options are limited, and the potential combination with other drugs, immune checkpoint inhibitors, CAR-T cells, CAR-NK, CAR-M, and vaccines is an interesting and appealing field that is still in development. In this review, we will discuss the highlights and pitfalls of the different HER2-targeted therapies and potential combinations to overcome metastatic disease and resistance to therapy.
    Language English
    Publishing date 2023-03-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15071987
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cancer immune exclusion: breaking the barricade for a successful immunotherapy.

    Bruni, Sofia / Mercogliano, María Florencia / Mauro, Florencia Luciana / Cordo Russo, Rosalia Inés / Schillaci, Roxana

    Frontiers in oncology

    2023  Volume 13, Page(s) 1135456

    Abstract: Immunotherapy has changed the course of cancer treatment. The initial steps were made through tumor-specific antibodies that guided the setup of an antitumor immune response. A new and successful generation of antibodies are designed to target immune ... ...

    Abstract Immunotherapy has changed the course of cancer treatment. The initial steps were made through tumor-specific antibodies that guided the setup of an antitumor immune response. A new and successful generation of antibodies are designed to target immune checkpoint molecules aimed to reinvigorate the antitumor immune response. The cellular counterpart is the adoptive cell therapy, where specific immune cells are expanded or engineered to target cancer cells. In all cases, the key for achieving positive clinical resolutions rests upon the access of immune cells to the tumor. In this review, we focus on how the tumor microenvironment architecture, including stromal cells, immunosuppressive cells and extracellular matrix, protects tumor cells from an immune attack leading to immunotherapy resistance, and on the available strategies to tackle immune evasion.
    Language English
    Publishing date 2023-05-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1135456
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Corrigendum: FXYD5/Dysadherin, a biomarker of endometrial cancer myometrial invasion and aggressiveness: its relationship with TGF-β1 and NF-κB pathways.

    Besso, María José / Rosso, Marina / Lapyckyj, Lara / Moiola, Cristian Pablo / Matos, María Laura / Mercogliano, María Florencia / Schillaci, Roxana / Reventos, Jaume / Colas, Eva / Gil-Moreno, Antonio / Wernicke, Alejandra / Orti, Roberto / Vazquez-Levin, Mónica Hebe

    Frontiers in oncology

    2024  Volume 13, Page(s) 1322204

    Abstract: This corrects the article DOI: 10.3389/fonc.2019.01306.]. ...

    Abstract [This corrects the article DOI: 10.3389/fonc.2019.01306.].
    Language English
    Publishing date 2024-01-23
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1322204
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  4. Article: Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer.

    Mercogliano, María Florencia / Bruni, Sofía / Elizalde, Patricia V / Schillaci, Roxana

    Frontiers in oncology

    2020  Volume 10, Page(s) 584

    Abstract: Breast cancer is the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women and represents a main problem for public health worldwide. Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine whose expression is ...

    Abstract Breast cancer is the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women and represents a main problem for public health worldwide. Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine whose expression is increased in a variety of cancers. In particular, in breast cancer it correlates with augmented tumor cell proliferation, higher malignancy grade, increased occurrence of metastasis and general poor prognosis for the patient. These characteristics highlight TNFα as an attractive therapeutic target, and consequently, the study of soluble and transmembrane TNFα effects and its receptors in breast cancer is an area of active research. In this review we summarize the recent findings on TNFα participation in luminal, HER2-positive and triple negative breast cancer progression and metastasis. Also, we describe TNFα role in immune response against tumors and in chemotherapy, hormone therapy, HER2-targeted therapy and anti-immune checkpoint therapy resistance in breast cancer. Furthermore, we discuss the use of TNFα blocking strategies as potential therapies and their clinical relevance for breast cancer. These TNFα blocking agents have long been used in the clinical setting to treat inflammatory and autoimmune diseases. TNFα blockade can be achieved by monoclonal antibodies (such as infliximab, adalimumab, etc.), fusion proteins (etanercept) and dominant negative proteins (INB03). Here we address the different effects of each compound and also analyze the use of potential biomarkers in the selection of patients who would benefit from a combination of TNFα blocking agents with HER2-targeted treatments to prevent or overcome therapy resistance in breast cancer.
    Language English
    Publishing date 2020-04-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.00584
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy.

    Mercogliano, María Florencia / Bruni, Sofía / Mauro, Florencia / Elizalde, Patricia Virginia / Schillaci, Roxana

    Cancers

    2021  Volume 13, Issue 3

    Abstract: Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine known to have contradictory roles in oncoimmunology. Indeed, TNFα has a central role in the onset of the immune response, inducing both activation and the effector function of macrophages, ... ...

    Abstract Tumor necrosis factor alpha (TNFα) is a pleiotropic cytokine known to have contradictory roles in oncoimmunology. Indeed, TNFα has a central role in the onset of the immune response, inducing both activation and the effector function of macrophages, dendritic cells, natural killer (NK) cells, and B and T lymphocytes. Within the tumor microenvironment, however, TNFα is one of the main mediators of cancer-related inflammation. It is involved in the recruitment and differentiation of immune suppressor cells, leading to evasion of tumor immune surveillance. These characteristics turn TNFα into an attractive target to overcome therapy resistance and tackle cancer. This review focuses on the diverse molecular mechanisms that place TNFα as a source of resistance to immunotherapy such as monoclonal antibodies against cancer cells or immune checkpoints and adoptive cell therapy. We also expose the benefits of TNFα blocking strategies in combination with immunotherapy to improve the antitumor effect and prevent or treat adverse immune-related effects.
    Language English
    Publishing date 2021-02-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13030564
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  6. Article ; Online: Corrigendum to "Novel role of signal transducer and activator of transcription 3 as a progesterone receptor coactivator in breast cancer" [Steroids 76 (2011) 381-392].

    Proietti, Cecilia J / Béguelin, Wendy / Díaz Flaqué, María Celeste / Cayrol, Florencia / Rivas, Martín A / Tkach, Mercedes / Charreau, Eduardo H / Schillaci, Roxana / Elizalde, Patricia V

    Steroids

    2023  Volume 200, Page(s) 109312

    Language English
    Publishing date 2023-10-01
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 80312-1
    ISSN 1878-5867 ; 0039-128X
    ISSN (online) 1878-5867
    ISSN 0039-128X
    DOI 10.1016/j.steroids.2023.109312
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  7. Article ; Online: Retraction Note: Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy.

    Flaqué, María C Díaz / Galigniana, Natalia M / Béguelin, Wendy / Vicario, Rocío / Proietti, Cecilia J / Russo, Rosalía Cordo / Rivas, Martín A / Tkach, Mercedes / Guzmán, Pablo / Roa, Juan C / Maronna, Esteban / Pineda, Viviana / Muñoz, Sergio / Mercogliano, María Florencia / Charreau, Eduardo H / Yankilevich, Patricio / Schillaci, Roxana / Elizalde, Patricia V

    Breast cancer research : BCR

    2023  Volume 25, Issue 1, Page(s) 133

    Language English
    Publishing date 2023-11-02
    Publishing country England
    Document type Retraction of Publication
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/s13058-023-01735-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Correction: Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer.

    Madera, Santiago / Izzo, Franco / Chervo, María F / Dupont, Agustina / Chiauzzi, Violeta A / Bruni, Sofia / Petrillo, Ezequiel / Merin, Sharon S / De Martino, Mara / Montero, Diego / Levit, Claudio / Lebersztein, Gabriel / Anfuso, Fabiana / Roldán Deamicis, Agustina / Mercogliano, María F / Proietti, Cecilia J / Schillaci, Roxana / Elizalde, Patricia V / Cordo Russo, Rosalía I

    Cell death & disease

    2023  Volume 14, Issue 12, Page(s) 833

    Language English
    Publishing date 2023-12-15
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2541626-1
    ISSN 2041-4889 ; 2041-4889
    ISSN (online) 2041-4889
    ISSN 2041-4889
    DOI 10.1038/s41419-023-06339-1
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  9. Article ; Online: Blocking soluble TNFα sensitizes HER2-positive breast cancer to trastuzumab through MUC4 downregulation and subverts immunosuppression.

    Bruni, Sofia / Mauro, Florencia L / Proietti, Cecilia J / Cordo-Russo, Rosalia I / Rivas, Martin A / Inurrigarro, Gloria / Dupont, Agustina / Rocha, Dario / Fernández, Elmer A / Deza, Ernesto Gil / Lopez Della Vecchia, Daniel / Barchuk, Sabrina / Figurelli, Silvina / Lasso, David / Friedrich, Adrián D / Santilli, María C / Regge, María V / Lebersztein, Gabriel / Levit, Claudio /
    Anfuso, Fabiana / Castiglione, Teresa / Elizalde, Patricia V / Mercogliano, Maria F / Schillaci, Roxana

    Journal for immunotherapy of cancer

    2023  Volume 11, Issue 3

    Abstract: Background: The success of HER2-positive (HER2+) breast cancer treatment with trastuzumab, an antibody that targets HER2, relies on immune response. We demonstrated that TNFα induces mucin 4 (MUC4) expression, which shields the trastuzumab epitope on ... ...

    Abstract Background: The success of HER2-positive (HER2+) breast cancer treatment with trastuzumab, an antibody that targets HER2, relies on immune response. We demonstrated that TNFα induces mucin 4 (MUC4) expression, which shields the trastuzumab epitope on the HER2 molecule decreasing its therapeutic effect. Here, we used mouse models and samples from HER2+ breast cancer patients to unravel MUC4 participation in hindering trastuzumab effect by fostering immune evasion.
    Methods: We used a dominant negative TNFα inhibitor (DN) selective for soluble TNFα (sTNFα) together with trastuzumab. Preclinical experiments were performed using two models of conditionally MUC4-silenced tumors to characterize the immune cell infiltration. A cohort of 91 patients treated with trastuzumab was used to correlate tumor MUC4 with tumor-infiltrating lymphocytes.
    Results: In mice bearing de novo trastuzumab-resistant HER2+ breast tumors, neutralizing sTNFα with DN induced MUC4 downregulation. Using the conditionally MUC4-silenced tumor models, the antitumor effect of trastuzumab was reinstated and the addition of TNFα-blocking agents did not further decrease tumor burden. DN administration with trastuzumab modifies the immunosuppressive tumor milieu through M1-like phenotype macrophage polarization and NK cells degranulation. Depletion experiments revealed a cross-talk between macrophages and NK cells necessary for trastuzumab antitumor effect. In addition, tumor cells treated with DN are more susceptible to trastuzumab-dependent cellular phagocytosis. Finally, MUC4 expression in HER2+ breast cancer is associated with immune desert tumors.
    Conclusions: These findings provide rationale to pursue sTNFα blockade combined with trastuzumab or trastuzumab drug conjugates for MUC4+ and HER2+ breast cancer patients to overcome trastuzumab resistance.
    MeSH term(s) Mice ; Animals ; Trastuzumab/pharmacology ; Trastuzumab/therapeutic use ; Down-Regulation ; Mucin-4/genetics ; Mucin-4/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Receptor, ErbB-2 ; Cell Line, Tumor ; Immunosuppression Therapy ; Neoplasms/drug therapy
    Chemical Substances Trastuzumab (P188ANX8CK) ; Mucin-4 ; Tumor Necrosis Factor-alpha ; Receptor, ErbB-2 (EC 2.7.10.1)
    Language English
    Publishing date 2023-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2022-005325
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  10. Article ; Online: ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.

    Elizalde, Patricia V / Cordo Russo, Rosalía I / Chervo, Maria F / Schillaci, Roxana

    Endocrine-related cancer

    2016  Volume 23, Issue 12, Page(s) T243–T257

    Abstract: Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC ... ...

    Abstract Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies.
    Language English
    Publishing date 2016-12
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 1218450-0
    ISSN 1479-6821 ; 1351-0088
    ISSN (online) 1479-6821
    ISSN 1351-0088
    DOI 10.1530/ERC-16-0360
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