癌症耐药(英文)最新文献

Head and neck cancer (HNC) is ranked as the sixth most common malignant tumor, and the overall survival rate with current treatment options remains concerning, primarily due to drug resistance that develops following antitumor therapy. Recent studies indicate that non-coding RNAs play a crucial role in drug resistance among HNC patients. This article systematically reviews the current research landscape, explores novel targets and treatment strategies related to non-coding RNAs and HNC resistance, raises some unresolved issues, and discusses five promising research directions in this field: ferroptosis, nanomedicine, exosomes, proteolysis-targeting chimeras (PROTACs), and artificial intelligence. We hope that our work will contribute to advancing research on overcoming HNC resistance through the regulation of non-coding RNAs.

Breast cancer is one of the most common cancers in women globally, posing significant challenges to treatment because of the diverse and complex pathological and molecular subtypes. The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of breast cancer, particularly for triple-negative breast cancer (TNBC), significantly improving patient outcomes. However, the overall tumor response rate remains suboptimal due to drug resistance to ICIs. This resistance is primarily due to the immune-suppressive tumor microenvironment (TME), tumor cells' ability to evade immune surveillance, and other complex immune regulatory mechanisms. To address these challenges, clinical researchers are actively exploring combinatorial therapeutic strategies with ICIs. Tumor local ablation (TLA) technology is anticipated to overcome resistance to ICIs and enhance therapeutic efficacy by ablating tumor tissue, releasing tumor antigens, remodeling the TME, and stimulating local and systemic immune responses. Combination therapy with TLA and ICIs has demonstrated promising results in preclinical breast cancer studies, underscoring the feasibility and importance of addressing drug resistance mechanisms in breast cancer. This provides novel strategies for breast cancer treatment and is expected to drive further advancements in the field.

Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.

Drug resistance in tumors constitutes a significant obstacle to tumor therapy. Head and neck squamous cell carcinoma (HNSCC) presents a major challenge due to its deep anatomical location, limited space, and complex structure. These factors complicate surgical procedures and hinder the effectiveness of chemoradiotherapy, leading to poor prognosis and reduced quality of life. However, there is hope in the form of circular RNAs (circRNAs), non-coding RNA molecules with a closed-loop structure that exhibits superior stability and resistance to degradation compared to linear RNAs. Recent advances in high-throughput sequencing and bioinformatics technology revealed that circRNAs participate in tumor proliferation, invasion, migration, and drug resistance. This review aims to summarize current research progress on the involvement of circRNAs in drug resistance of HNSCC and provide valuable insights for the prevention and mitigation of drug resistance in HNSCC.

MicroRNAs (miRNAs) are small non-coding RNAs comprising 19-24 nucleotides that indirectly control gene expression. In contrast to other non-coding RNAs (ncRNAs), circular RNAs (circRNAs) are defined by their covalently closed loops, forming covalent bonds between the 3' and 5' ends. circRNAs regulate gene expression by interacting with miRNAs at transcriptional or post-transcriptional levels. Accordingly, circRNAs and miRNAs control many biological events related to cancer, including cell proliferation, metabolism, cell cycle, and apoptosis. Both circRNAs and miRNAs are involved in the pathogenesis of diseases, such as breast cancer. This review focuses on the latest discoveries on dysregulated circRNAs and miRNAs related to breast cancer, highlighting their potential as biomarkers for clinical diagnosis, prognosis, and chemotherapy response.

The ABCB5 gene encodes several isoforms, including two transporters (i.e., ABCB5FL, ABCB5β) and several soluble proteins, such as ABCB5α which has been hypothesized to have a regulatory function. ABCB5FL is a full ABC transporter and is expressed in the testis and prostate, whereas ABCB5β is an atypical half-transporter with a ubiquitous expression pattern. ABCB5β has been shown to mark cancer stem cells in several cancer types. In addition, ABCB5β and ABCB5FL have been shown to play a role in tumorigenesis and multidrug resistance. However, ABCB5β shares its entire protein sequence with ABCB5FL, making them difficult to distinguish. It cannot be excluded that some biological effects described for one transporter may be mediated by the other isoform. Therefore, it is difficult to interpret the available data and some controversies remain regarding their function in cancer cells. In this review, we discuss the data collected on ABCB5 isoforms over the last 20 years and propose a common ground on which we can build further to unravel the pathophysiological roles of ABCB5 transporters.

Despite significant advances in the understanding of multiple myeloma (MM) biology and the development of novel treatment strategies in the last two decades, MM is still an incurable disease. Novel drugs with alternative mechanisms of action, such as selective inhibitors of nuclear export (SINE), modulators of the ubiquitin pathway [cereblon E3 ligase modulatory drugs (CELMoDs)], and T cell redirecting (TCR) therapy, have led to significant improvement in patient outcomes. However, resistance still emerges, posing a major problem for the treatment of myeloma patients. This review summarizes current data on treatment with SINE, TCR therapy, and CELMoDs and explores their mechanism of resistance. Understanding these resistance mechanisms is critical for developing strategies to overcome treatment failure and improve therapeutic outcomes.

Aim: This study aimed to investigate drug candidates and their efficacy in treating refractory multiple myeloma (MM) despite significant therapeutic advances and the introduction of novel agents. Our study focused on how myeloma cells mediate the metabolic pathways essential for survival. Therefore, we examined the role of glutaminolysis in this process. Methods: We investigated the role of glutaminolysis in myeloma cell growth. In addition, we analyzed the ability of CB-839 (telaglenastat), a glutaminase (GLS) inhibitor, to suppress myeloma cell proliferation and enhance the sensitivity to histone deacetylase (HDAC) inhibitors. Results: Glutamate deprivation significantly reduced MM cell proliferation. We observed an upregulation of GLS1 expression in MM cell lines compared to that in normal controls. CB-839 inhibits MM cell proliferation in a dose-dependent manner, resulting in enhanced cytotoxicity. Additionally, intracellular α-ketoglutarate and nicotinamide adenine dinucleotide phosphate levels decreased after CB-839 administration. Combining panobinostat with CB-839 resulted in enhanced cytotoxicity and increased caspase 3/7 activity. Cells transfected with GLS shRNA exhibited reduced cell viability and elevated sub-G1 phase according to cell cycle analysis results. Compared to control cells, these cells also showed increased sensitivity to panobinostat. Conclusion: Glutaminolysis contributes to the viability of MM cells, and the GLS inhibitor CB-839 has been proven to be an effective treatment for enhancing the cytotoxic effect of HDAC inhibition. These results are clinically relevant and suggest that CB-839 is a potential therapeutic candidate for patients with MM.

The increasing prevalence of cancer drug resistance not only critically limits the efficiency of traditional therapies but also causes relapses or recurrences of cancer. Consequently, there remains an urgent need to address the intricate landscape of drug resistance beyond traditional cancer therapies. Recently, nanotechnology has played an important role in the field of various drug delivery systems for the treatment of cancer, especially therapy-resistant cancer. Among advanced nanomedicine technologies, lipid-based nanomaterials have emerged as effective drug carriers for cancer treatment, significantly improving therapeutic effects. Due to their biocompatibility, simplicity of preparation, and potential for functionalization, lipid-based nanomaterials are considered powerful competitors for resistant cancer. In this review, an overview of lipid-based nanomaterials for addressing cancer resistance is discussed. We summarize the recent progress in overcoming drug resistance in cancer by these lipid-based nanomaterials, and highlight their potential in future applications to reverse cancer resistance.

Decades ago, the viral myeloblastosis oncogene v-myb was identified as a gene responsible for the development of avian leukemia. However, the relevance of MYB proteins for human cancer diseases, in particular for solid tumors, remained basically unrecognized for a very long time. The human family of MYB transcription factors comprises MYB (c-MYB), MYBL2 (b-MYB), and MYBL1 (a-MYB), which are overexpressed in several cancers and are associated with cancer progression and resistance to anticancer drugs. In addition to overexpression, the presence of activated MYB-fusion proteins as tumor drivers was described in certain cancers. The identification of anticancer drug resistance mediated by MYB proteins and their underlying mechanisms are of great importance in understanding failures of current therapies and establishing new and more efficient therapy regimens. In addition, new drug candidates targeting MYB transcription factor activity and signaling have emerged as a promising class of potential anticancer therapeutics that could tackle MYB-dependent drug-resistant cancers in a more selective way. This review describes the correlation of MYB transcription factors with the formation and persistence of cancer resistance to various approved and investigational anticancer drugs.