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Therapeutic implications of the molecular and immune landscape of triple-negative breast cancer

Publication . Gregório, Ana C.; Lacerda, Manuela; Figueiredo, Paulo; Simões, Sérgio; Dias, Sérgio; Moreira, João Nuno

Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient's prognosis and increased the predictive power to therapeutic response and clinical outcome. Molecular heterogeneity is also prominent in the triple-negative breast cancer subtype, and is reflected by the distinct prognostic and patient's sensitivity to treatment, being chemotherapy the only systemic treatment currently available. From a therapeutic perspective, gene expression profiling of triple-negative tumors has notably contributed to the exploration of new druggable targets and brought to light the need to align these patients to the various therapies according to their triple-negative subtype. Additionally, the higher amount of tumor infiltrating lymphocytes, and the prevalence of an increased expression of PD-1 receptor and its ligand, PD-L1, in triple-negative tumors, created a new treatment opportunity with immune checkpoint inhibitors. This manuscript addresses the current knowledge on the molecular and immune profiles of breast cancer, and its impact on the development of targeted therapies, with a particular emphasis on the triple-negative subtype.

2018-10Journal article

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Meeting the needs of breast cancer: a nucleolin’s perspective

Publication . Gregório, Ana C.; Lacerda, Manuela; Figueiredo, Paulo; Simões, Sérgio; Dias, Sérgio; Moreira, João Nuno

A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.

2018Journal article

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