Medical Oncology最新文献

Epigenetic modulators have recently emerged as potential targets in cancer therapy. Breast cancer, the second leading cause of cancer-related deaths among women globally and the most common cancer in India, continues to have a low survival rate despite available treatments. This underscores the urgent need for more effective therapeutic strategies. Histone deacetylases (HDACs), a prominent class of epigenetic modulators, are frequently overexpressed in various cancers, including breast cancer, making them and their downstream pathways, a focus of current research, aiming to develop more effective and less invasive treatments that could help overcome chemoresistance and enhance patient outcomes. Despite the growing body of evidences, a comprehensive and consolidated review on molecular intricacy behind the HDAC-mediated epigenetic regulation of breast cancer is conspicuously absent. Therefore, this review aims to open doors for future research by exploring the evolving role of HDACs, their molecular mechanisms, and their potential as therapeutic targets in breast cancer treatment.

Lung cancer ranks among the most lethal types of cancer globally, with a high occurrence and fatality rate. The spread of cancer to other parts of the body, known as metastasis, is the primary cause of treatment failure and death in lung cancer cases. Current approaches for treating advanced lung cancer typically involve a combination of chemotherapy and targeted therapy. However, the majority of patients ultimately develop resistance to these treatments, leading to a worsened prognosis. In recent years, cancer biology research has predominantly focused on the role of protein-encoding genes in cancer development. Long non-coding RNAs (lncRNAs) are transcripts over 200 nucleotides in length that do not encode proteins but are crucial RNA molecules involved in numerous biological functions. While many functions of lncRNAs remain unknown, some have been linked to human diseases, including cancer. Studies have demonstrated that lncRNAs interact with other large molecules in the cell, such as proteins, DNA, and RNA, influencing various critical aspects of cancer. LncRNAs play a significant role in regulating gene expression and have a crucial function in the transcriptional regulation of cancer cells. They mediate various biological and clinical processes such as invasion, metastasis, apoptosis, and cell proliferation. Dysregulation of lncRNAs has been found to impact the process of carcinogenesis through advanced technologies like RNA sequencing and microarrays. Collectively, these long non-coding RNAs hold promise as potential biomarkers and therapeutic targets for human cancers. In this segment, we provide a comprehensive summary of the literature on the characteristics and formation of lncRNAs, along with an overview of their current known roles in lung cancer.

Radiotherapy is important in treating esophageal squamous cell carcinoma (ESCC) comprehensively. Resistance to radiotherapy is a prominent factor contributing to treatment failure in patients with ESCC. The objective of this study was to investigate the impact of ML385, an inhibitor of nuclear factor erythroid 2-related factor 2 (NRF2), on the radiosensitivity of ESCC and elucidate its underlying mechanism. We treated KYSE150 and KYSE510 cells with ML385 and ionising radiation separately or simultaneously, and observed the proliferation, apoptosis, cell cycle and ferroptosis of different conditions by colony formation assay and flow cytometry. Our findings reveal that NRF2 was activated by radiation and translocated from the cytoplasm to the nucleus after radiation. However, ML385 inhibited the expression and cytoplasm-to-nucleus translocation of NRF2. Compared with radiation, ML385 combined with radiation exhibited a significant inhibition on the clone formation ability of ESCC cells, induced apoptosis and promoted G2/M phase arrest. The treatment of ML385 combined with radiation markedly increased ROS and lipid peroxidation levels and decreased glutathione levels compared with the control, thus promoting the occurrence of ferroptosis. In addition, the expression trend of NRF2 was the same as that of proteins related ferroptosis, such as SLC7A11 and GPX4. After overexpression of SLC7A11, we found that significantly restored glutathione levels and alleviated ML385 combined with radiation-induced lipid peroxidation, indicating that ML385 plays a key role in radiotherapy sensitization by inhibiting the NRF2-SLC7A11 pathway. In vivo, ML385 also promoted the killing effect of radiation on xenografted tumours in nude mice. This study identifies NRF2 inhibitor ML385 as a radiosensitizer of ESCC, which highlights the therapeutic potential of the NRF2-SLC7A11 pathway and provides a deeper understanding of the mechanism of ferroptosis in esophageal squamous cell carcinoma.

The CAP (Cysteine-rich secretory protein, Antigen 5, and Pathogenesis-related protein 1) superfamily proteins (CAP proteins) are found in all kingdoms of life. The cysteine-rich secreted proteins are prevalent in human organs and tissues and serve as critical signaling molecules within cells, regulating a wide range of biochemical processes in the human body. Due to their involvement in numerous biological processes, CAP proteins have recently attracted significant attention, particularly in the context of tumorigenesis and cancer therapy. This review summarizes the expression patterns and roles of CAP proteins in various cancers. Additionally, it analyzes the mechanisms by which CAP proteins affect cancer cell proliferation and survival, regulate epithelial-mesenchymal transition, influence drug resistance, and regulate epigenetics. The review reveals that CAP proteins play distinct roles in various signaling pathways, such as the MAPK, PI3K-Akt, and p53 pathways, which are crucial for tumor progression. Furthermore, this review summarizes the tumor-inhibiting function of CAP proteins and their potential as cancer biomarkers. These findings suggest that CAP proteins represent a promising new target for innovative cancer diagnosis and treatment.

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance. Trastuzumab could induce G1/G0 phase arrest by downregulating cyclin D3 protein expression. However, the protein expression of cyclin D3 was not affected in trastuzumab-resistant cells, which might be related to aberrant activation of ERK signaling pathway. Furthermore, degradation of cyclin D3 protein by trastuzumab was mainly resulted from ubiquitin-dependent proteasome mechanism instead of transcriptional regulation. In trastuzumab-resistant breast cancer cells, trastuzumab-induced degradation of cyclin D3 protein was abrogated. When the ubiquitin pathway was inhibited, cells would show a predisposition to resistance to trastuzumab. Further, CDK4/6 inhibitor can inhibit the proliferation of trastuzumab-resistant HER-2 positive breast cancer cells. Therefore, combination of CDK4/6 inhibitors and anti-HER2 targeted therapy may be an alternative and promising strategy to overcome trastuzumab resistance in the future.

This document was drafted by interdisciplinary experts informed by the evidence and guided by their extensive lymphedema clinical experience at the 2023 American Cancer Society (ACS) Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management hosted by the ACS, Lymphology Association of North America, and the Washington School of Medicine  in St. Louis, Missouri. Consensus statements were derived from a facilitated workshop and multiple follow-up discussions and meetings combining available evidence and clinical expertise. The consensus statements find that the essential components of complete decongestive therapy (CDT) are examination, compression, manual techniques (this may include but is not limited to manual lymph drainage), exercise, skin care, education, and self-management. Adjunctive interventions and alternatives may complement CDT. CDT should be provided by specifically trained healthcare practitioners in lymphedema management, preferably a certified lymphedema therapist. The individual's lymphedema etiology and presentation, comorbidities, and other pertinent clinical information will determine the components of CDT applied and the frequency and duration of care.

Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.

Hepatocellular carcinoma (HCC) is a leading liver cancer that significantly impacts global life expectancy and remains challenging to treat due to often late diagnoses. Despite advances in treatment, the prognosis is still poor, especially in advanced stages. Studies have pointed out that investigations into the molecular mechanisms underlying HCC, including mitochondrial dysfunction and epigenetic regulators, are potentially important targets for diagnosis and therapy. Mitoepigenetics, or the epigenetic modifications of mitochondrial DNA, have drawn wide attention for their role in HCC progression. Besides, molecular biomarkers such as mitochondrial DNA alterations and non-coding RNAs showed early diagnosis and prognosis potential. Additionally, natural compounds like alkaloids, resveratrol, curcumin, and flavonoids show promise in HCC show promise in modulating mitochondrial and epigenetic pathways involved in cancer-related processes. This review discusses how mitochondrial dysfunction and epigenetic modifications, especially mitoepigenetics, influence HCC and delves into the potential of natural products as new adjuvant treatments against HCC.