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  • 11
    Online Resource
    Online Resource
    Molecular Mechanisms of Resistance to Immunotherapy and Antiangiogenic Treatments in Clear Cell Renal Cell Carcinoma
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 23 ( 2021-11-28), p. 5981-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 23 ( 2021-11-28), p. 5981-
    Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype arising from renal cell carcinomas. This tumor is characterized by a predominant angiogenic and immunogenic microenvironment that interplay with stromal, immune cells, and tumoral cells. Despite the obscure prognosis traditionally related to this entity, strategies including angiogenesis inhibition with tyrosine kinase inhibitors (TKIs), as well as the enhancement of the immune system with the inhibition of immune checkpoint proteins, such as PD-1/PDL-1 and CTLA-4, have revolutionized the treatment landscape. This approach has achieved a substantial improvement in life expectancy and quality of life from patients with advanced ccRCC. Unfortunately, not all patients benefit from this success as most patients will finally progress to these therapies and, even worse, approximately 5 to 30% of patients will primarily progress. In the last few years, preclinical and clinical research have been conducted to decode the biological basis underlying the resistance mechanisms regarding angiogenic and immune-based therapy. In this review, we summarize the insights of these molecular alterations to understand the resistance pathways related to the treatment with TKI and immune checkpoint inhibitors (ICIs). Moreover, we include additional information on novel approaches that are currently under research to overcome these resistance alterations in preclinical studies and early phase clinical trials.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13235981
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 12
    Online Resource
    Online Resource
    Bronchial Carcinoids: From Molecular Background to Treatment Approach
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 3 ( 2022-01-20), p. 520-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 3 ( 2022-01-20), p. 520-
    Abstract: A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14030520
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 13
    Online Resource
    Online Resource
    Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance
    MDPI AG ; 2021
    In:  Biomedicines Vol. 9, No. 3 ( 2021-03-16), p. 304-
    Details
    In: Biomedicines, MDPI AG, Vol. 9, No. 3 ( 2021-03-16), p. 304-
    Abstract: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines9030304
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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