RESUMO
LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor. Here, we focus on the mechanisms through which LOXL2 orchestrates multiple oncogenic functions in HCC development. We performed a review of the current knowledge on the roles LOXL2 performs in the modulation of the HCC tumor microenvironment, formation of premetastatic niches, and epithelial-mesenchymal transition. We also highlighted the complex interplay between LOXL2 and hypoxia, angiogenesis, and vasculogenic mimicry in HCC. At the end of the review, we summarize the current LOXL2 inhibitors and discuss their potential in HCC precision treatment.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fenótipo , Morfogênese , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral/genéticaRESUMO
The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 < 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence > 1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6-6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1-10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61-0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4-20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59-0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.
Assuntos
Antineoplásicos Imunológicos , Neoplasias da Mama , Imunoconjugados , Ado-Trastuzumab Emtansina , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Feminino , Hormônios/uso terapêutico , Humanos , Imunoconjugados/uso terapêutico , Antígeno Ki-67 , Lapatinib/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/uso terapêutico , Trastuzumab/uso terapêuticoRESUMO
PURPOSE: Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines. METHODS: The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records. RESULTS: During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported. CONCLUSION: We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.