The medical treatment of breast cancer (BC) and soft tissues sarcomas (STS) represents an interesting field of research for both preclinical laboratory investigations and clinical studies. The improved knowledge of the relationship between cancer cells and their microenvironment has led to the identification of new potential targets of therapy. Hence, in recent years many drugs have been found to improve survival of patients with such malignancies, which are both currently considered as heterogeneous diseases requiring tailored therapies and a multidisciplinary management. Tumor growth is a dynamic balance between cellular development and apoptosis, but apoptosis signaling mechanisms are impaired in cancer cells, leading to multidrug resistance. Thus, new individualized therapeutic strategies must be continuously developed with the purpose of antagonizing resistance mechanisms that regulate metabolic actions of cancer cells. central reservoir for their formation. Thus, both aromatase inhibitors (AIs) and steroid sulfatase inhibitors may be used in the adjuvant treatment of patients with estrogen receptor (ER)-positive BC, which are currently classified as luminal A and luminal B subtypes according to their gene expression pattern. Endocrine therapy alone or in combination with cytotoxic drugs represents the targeted therapy of choice in such tumors. It mainly consists of selective ER modulators (SERMs) or down-regulators, and AIs administration. Tamoxifen is a competitive nonsteroidal inhibitor of estradiol at its receptor on BC cells, partial estrogen agonist in the liver, bone and uterus, and the bestestablished SERM. HER2+ tumors may be ER and progesterone receptor (PR) positive or negative. Patients with HER2+ BC can be treated with the anti-HER2 monoclonal antibody trastuzumab. The so-called triple negative (HER2-/ER-/PR-) BC is usually an aggressive tumor with rapid growth, high rate of node positivity, high incidence of distant metastasis, and overall poor survival compared with that in patients who have other phenotypes. Soft tissue sarcomas are rare tumors, accounting for about 10% and 1% of cancers in children and adults, respectively. About 40% of STS occur in the legs, but they can also often localize in the abdomen and retroperitoneum. The usefulness of adjuvant chemotherapy to treat adults with localized resectable STSs remains controversial, and several studies confirm its marginal efficacy in respect of local and distant recurrence. However, the early administration of cytotoxic drugs might improve the overall survival of patients. According to the ESMO (European Society for Medical Oncology) guidelines, the standard chemotherapy is based on anthracyclines (i.e., doxorubicin) alone or in combination with ifosfamide as first-line treatment, and ifosfamide alone may be used as second-line chemotherapy. Synergistic antitumor activity has also been demonstrated with combination blockade of mTOR and insulin-like growth factor 1 receptor (IGF-1R) signaling by mTOR inhibitors (i.e., everolimus) and human monoclonal antibody anti IGF1-R (i.e., figitumumab). Isolated patients with particular type of STS (i.e., inflammatory myofibroblastic tumor or metastatic sarcoma) may respond to specific therapies, such as anaplastic lymphoma kinase (ALK) inhibitor (i.e., crizotinib) or antiangiogenetic drugs (i.e., sorafenib).

Editorial: Targeted therapies in the treatment of breast cancer and localized sarcomas.

LUMACHI, FRANCO
2013

Abstract

The medical treatment of breast cancer (BC) and soft tissues sarcomas (STS) represents an interesting field of research for both preclinical laboratory investigations and clinical studies. The improved knowledge of the relationship between cancer cells and their microenvironment has led to the identification of new potential targets of therapy. Hence, in recent years many drugs have been found to improve survival of patients with such malignancies, which are both currently considered as heterogeneous diseases requiring tailored therapies and a multidisciplinary management. Tumor growth is a dynamic balance between cellular development and apoptosis, but apoptosis signaling mechanisms are impaired in cancer cells, leading to multidrug resistance. Thus, new individualized therapeutic strategies must be continuously developed with the purpose of antagonizing resistance mechanisms that regulate metabolic actions of cancer cells. central reservoir for their formation. Thus, both aromatase inhibitors (AIs) and steroid sulfatase inhibitors may be used in the adjuvant treatment of patients with estrogen receptor (ER)-positive BC, which are currently classified as luminal A and luminal B subtypes according to their gene expression pattern. Endocrine therapy alone or in combination with cytotoxic drugs represents the targeted therapy of choice in such tumors. It mainly consists of selective ER modulators (SERMs) or down-regulators, and AIs administration. Tamoxifen is a competitive nonsteroidal inhibitor of estradiol at its receptor on BC cells, partial estrogen agonist in the liver, bone and uterus, and the bestestablished SERM. HER2+ tumors may be ER and progesterone receptor (PR) positive or negative. Patients with HER2+ BC can be treated with the anti-HER2 monoclonal antibody trastuzumab. The so-called triple negative (HER2-/ER-/PR-) BC is usually an aggressive tumor with rapid growth, high rate of node positivity, high incidence of distant metastasis, and overall poor survival compared with that in patients who have other phenotypes. Soft tissue sarcomas are rare tumors, accounting for about 10% and 1% of cancers in children and adults, respectively. About 40% of STS occur in the legs, but they can also often localize in the abdomen and retroperitoneum. The usefulness of adjuvant chemotherapy to treat adults with localized resectable STSs remains controversial, and several studies confirm its marginal efficacy in respect of local and distant recurrence. However, the early administration of cytotoxic drugs might improve the overall survival of patients. According to the ESMO (European Society for Medical Oncology) guidelines, the standard chemotherapy is based on anthracyclines (i.e., doxorubicin) alone or in combination with ifosfamide as first-line treatment, and ifosfamide alone may be used as second-line chemotherapy. Synergistic antitumor activity has also been demonstrated with combination blockade of mTOR and insulin-like growth factor 1 receptor (IGF-1R) signaling by mTOR inhibitors (i.e., everolimus) and human monoclonal antibody anti IGF1-R (i.e., figitumumab). Isolated patients with particular type of STS (i.e., inflammatory myofibroblastic tumor or metastatic sarcoma) may respond to specific therapies, such as anaplastic lymphoma kinase (ALK) inhibitor (i.e., crizotinib) or antiangiogenetic drugs (i.e., sorafenib).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2577700
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