Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.

Despite the options available for breast cancer (BC) therapy, several adverse effects and resistance limit the success of the treatment. Furthermore, the use of a single drug is associated with a high failure rate. We investigated through a systematic review the in vitro effects of the combination between conventional drugs and bioactive compounds derived from cinnamic acid in BC treatment. The information was acquired from the following databases: PubMed, Web of Science, Embase, Scopus, Lilacs and Cochrane library. We focused on “Cinnamates”, “Drug Combinations” and “Breast neoplasms” for publications dating between January 2012 and December 2022, based on the PRISMA statement. The references of the articles were carefully reviewed. Finally, nine eligible studies were included. The majority of these studies were performed using MCF-7, MDA-MB-231, MDA-MB-468 and BT-20 cell lines and the combination between cisplatin, paclitaxel, doxorubicin, tamoxifen, dactolisib and veliparib, with caffeic acid phenethyl ester, eugenol, 3-caffeoylquinic acid, salvianolic acid A, ferulic acid, caffeic acid, rosmarinic acid and ursolic acid. The combination improved overall conventional drug effects, with increased cytotoxicity, antimigratory effect and reversing resistance. Combining conventional drugs with bioactive compounds derived from cinnamic acid could emerge as a privileged scaffold for establishing new treatment options for different BC types.

Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

INTRODUÇÃO: O câncer cervical é um sério problema de saúde entre as mulheres, principalmente em países de baixa renda. A detecção e o tratamento precoce são fundamentais para o melhor prognóstico e aumentam substancialmente as taxas de cura da doença. Nesse cenário, os biomarcadores podem ser úteis para o rastreio, diagnóstico, avaliação do prognóstico, da resposta à terapia e detecção precoce de recorrência após o tratamento do câncer cervical. Diversos biomarcadores vêm sendo investigados, mas poucas opções estão disponíveis para aplicação clínica. OBJETIVOS: Revisar os estudos clínicos acerca de biomarcadores para o CC publicados nos últimos 10 anos, com foco no diagnóstico, prognóstico e avaliação do tratamento. METODOLOGIA: As bases de dados PubMed, Web of Science e Science Direct foram pesquisadas utilizando os descritores “Uterine Cervical Neoplasms” e "Biomarkers". Foram selecionados os artigos originais publicados em inglês ou português, no período de 2011 a 2021. Após uma triagem pelos títulos e resumos dos artigos, aqueles relacionados ao objetivo do estudo foram lidos integralmente para a decisão final de inclusão na revisão. Os trabalhos que atenderam todos os critérios de seleção tiveram seus dados extraídos, principalmente no que se refere ao tipo e objetivo do biomarcador proposto, população de estudo, tamanho da amostra, metodologia utilizada e principais desfechos obtidos. RESULTADOS: Essa estratégia de busca e seleção resultou em 22 artigos publicados nos últimos 10 anos na temática de interesse. Houve um grande empenho na investigação de biomarcadores séricos para o câncer cervical, com a vantagem de serem minimamente invasivos. Houve destaque para marcadores genéticos e moleculares, como aqueles voltados para a metilação do DNA, detecção de polimorfismos, padrões de expressão de microRNAs e expressão de genes relacionados à proliferação, imortalização e invasão celular. CONCLUSÃO: Os dados reunidos encorajam a ampliação das pesquisas para aprimorar e validar a eficiência destes biomarcadores em grandes populações. É evidente o potencial dos biomarcadores como estratégia para melhorar o manejo do diagnóstico e tratamento do câncer cervical, sendo que a utilização de marcadores genéticos parece ser o futuro dos biomarcadores para o câncer cervical.

A small subset of cervical cancers tests negative for human Papillomavirus (HPV) DNA, being associated with poorer prognosis and higher aggressiveness. This study systematically reviewed the current status of HPV DNA-independent cervical cancers from clinical, diagnostic and prognostic perspectives, in comparison to HPV-associated cervical cancers. Relevant terms were searchedin databases including PubMed, EMBASE, LILACS, Web of Science, Scopus, CINAHL and the Cochrane Controlled Trials Registered between January 2018 and December 2023. We focused on studies published in peer-reviewed English-language with available abstracts. Researchers independently screened the titles and abstracts and the selected articles were then read in full text. After reaching a consensus, 31 papers were selected for data extraction. Various techniques were employed for HPV testing, primarily based on polymerase chain reaction (PCR) and different types of clinical samples were analyzed. A total of 9.2% of the cases were found to be HPV-negative (mean age of 55.8 years). HPV-independent cervical cancers exhibit distinct characteristics; however, several challenges in interpreting the data were identified. Our findings demonstrate the difficulty in distinguishing truly HPV-independent cervical cancers from false-negative ones. Moreover, there is a critical need for new, more comprehensive and rigorously controlled studies to better elucidate the complexities surrounding HPV-independent cervical cancers.