Anti-cancer agents in medicinal chemistry最新文献

Amino acid-based PET tracers have become vital tools for non-invasive tumor imaging, offering greater specificity and sensitivity than conventional 18F-FDG. These tracers target amino acid transporters, particularly L-type Amino Acid Transporter 1 (LAT1), which is overexpressed in rapidly proliferating tumor cells. Various 18F-labeled amino acid tracers have been explored for imaging different malignancies, including gliomas, neuroendocrine tumors, and lung cancers. This review summarizes the performance of LAT1-specific radiotracers, comparing their uptake ratios, sensitivity, and specificity in cancer diagnosis. These tracers have led to significant advancements in tumor imaging, providing better diagnostic accuracy, enhanced tumor delineation, and reduced interference from inflammatory tissue. Although promising, the clinical utility of these tracers requires further research and clinical trials to refine their applications and optimize their role in routine clinical practice. Continued development will be crucial in making these tracers more effective and widely applicable for cancer diagnosis and treatment planning.

Chimeric Antigen Receptor T-cell (CAR-T) therapy represents a pioneering advancement in immunotherapy, demonstrating substantial clinical success in the treatment of hematologic malignancies, particularly in B-cell hematologic malignancies. This therapeutic approach involves the genetic modification of a patient's Tcells to express receptors specific to tumor antigens, thereby enabling the CAR T-cells to identify and eradicate tumor cells, which significantly enhances the patient's treatment prognosis. Despite the remarkable efficacy of CAR-T therapy, concerns regarding its safety have emerged during clinical implementation. Notably, research has indicated that CAR T-cell therapy may be associated with the development of secondary primary malignancies, prompting considerable apprehension within the clinical community regarding the long-term adverse effects of this treatment modality. This article aims to investigate the potential mechanisms responsible for the induction of secondary primary malignancies by CAR T-cells, evaluate the associated risk factors, and discuss therapeutic strategies to mitigate this issue. Furthermore, the article will explore future research directions focused on optimizing the safety profile of CAR-T therapy, thereby providing a theoretical foundation for the development of safer and more effective therapeutic interventions.

Background: The smooth muscle α‑actin 2‑antisense 1 (ACTA2-AS1), also known as ZXF1, is an emerging cancer-associated long non-coding RNA (lncRNA) that has garnered significant attention in recent years. ACTA2-AS1 is situated on human chromosome 10 at location 10q23.31, comprising five exons and a single transcript. The aberrant expression of ACTA2-AS1 has been noted in 10 malignant tumors, correlating significantly with unfavorable clinicopathological characteristics and poor patient prognosis.

Objective: This review encapsulates recent progress in ACTA2-AS1 research, examining its expression profile, biological functions, molecular mechanisms, and anticipated influence on cancer diagnosis, treatment, and prognosis, emphasizing its potential as a novel therapeutic target based on lncRNA and its prognostic utility as a biomarker.

Methods: Based on a comprehensive search of the PubMed database for the biological function of lncRNA ACTA2-AS1 in malignant tumors, the current research is systematically summarized and critically analyzed.

Results: ACTA2-AS1 plays a complex role in various biological processes in tumor cells, encompassing proliferation, apoptosis, and cell cycle arrest. It also contributes to migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. Mechanistically, ACTA2-AS1 influences oncogenic or tumor-suppressive effects via a complex regulatory network. It can adsorb specific 5 miRNAs as competitive endogenous RNAs (ceRNAs), thereby mitigating the suppression of downstream mRNA targets implicated in tumorigenesis (e.g., SOX7, KLF9, CXCL2, BCL2L11, etc.) and modulating their downstream signaling pathways (e.g., Wnt5a/PKC, SMAD3, mTOR, etc.), demonstrating a broad spectrum of dual roles in carcinogenesis and tumor suppression.

Conclusion: ACTA2-AS1 is a promising biomarker and molecular target for the treatment of cancer.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies in the world. To overcome clinical challenges, such as high postoperative recurrence rates and prominent resistance to chemotherapy, new therapeutic strategies are urgently needed. Phototherapy, particularly Photodynamic Therapy (PDT) and Photothermal Therapy (PTT), has unique advantages in selectively killing tumor cells. However, traditional Photosensitizers (PSs) and Photothermal Agents (PTAs) have inherent defects, such as limited tissue penetration depth, poor optical stability, and insufficient targeting ability, which severely restrict phototherapy in clinical applications. Significant advancements have been made in enhancing the phototherapeutic effects of metal nanomaterials in recent years. This progress can be attributed to their tunable optical properties, exceptional Photothermal Conversion Efficiency (PCE), and unique Surface Plasmon Resonance (SPR) effects. In this review, we systematically summarized the latest progress in research on the use of metal nanomaterials for the optical diagnosis and treatment of colorectal cancer. We focused on the mechanism by which typical nanomaterials such as gold, silver, and platinum enhance the therapeutic effect of PDT/PTT. Additionally, a comprehensive analysis was conducted to evaluate the application and potential of nano-optical sensitizers incorporating metallic cores such as gold, silver, iridium, platinum, iron, zinc, copper, ruthenium, and titanium for the diagnosis and treatment of Colorectal Cancer (CRC). This review may provide theoretical guidance for developing new-generation optical diagnostic and therapeutic strategies for treating colorectal cancer.

Natural coumarins, a class of compounds found abundantly in various plants, are emerging as promising candidates in fight against cancer. Their ability to target multiple cancer-related processes has drawn significant interest from researchers. Natural coumarins exhibit anticancer effects through mechanisms such as inducing apoptosis, which is the programmed death of cancer cells, inhibiting cell proliferation, and disrupting angiogenesis, the process by which tumors develop their own blood supply to sustain growth. What makes coumarins particularly intriguing is their broad-spectrum activity against various types of cancer cells, from breast to lung to colon cancers. They interact with key molecular pathways that drive tumor progression, making them versatile agents in cancer therapy. Additionally, unlike many conventional chemotherapy drugs, natural coumarins generally have lower toxicity, which could translate to fewer side effects for patients. This characteristic makes them attractive as potential standalone treatments or as complementary therapies that enhance the efficacy of existing drugs while minimizing harm to normal cells. Ongoing research continues to explore the therapeutic potential of natural coumarins to better understand their full therapeutic potential and how they might work in combination with other anticancer agents. As the body of evidence grows, these natural compounds could become integral components of more effective and less harmful cancer treatment regimens, offering new hope for patients facing this challenging disease. This review was conducted by systematically analyzing the existing literature on natural coumarins and their anticancer potential.

Background: PD-L1 plays a pivotal role as an immunoregulatory checkpoint within the immune system, exerting a critical influence on the internal functioning and survival mechanisms of cancer cells. This study aimed to elucidate the clinical significance of PD-L1 expression in Circulating Tumor Cells (CTCs) derived from individuals afflicted with Hypopharyngeal and Laryngeal Cancers (HLC), as well as its potential implications for clinical practice.

Objective: The aim of this study was to verify the relationship between the expression of PD-L1 in CTCs in HLC and the consistency in tissue and the preliminary clinical application.

Methods: A laboratory-based experimental study was carried out at Fujian Medical University Union Hospital. CTCs were identified using an immunomagnetic positive sorting methodology. Simultaneous detection was conducted on the CTC levels among PD-L1 positive patients, aiming to ascertain the dynamic relationship between real-time CTC fluctuations and the clinicopathological indices of the patients. This investigation encompassed a cohort of 38 individuals, wherein PD-L1 expression analysis was executed to delineate CTC variations in PD-L1- positive patients.

Results: The constructed immunolipid magnetic nano-beads demonstrated pronounced efficacy in capturing CTCs, and the lipid nanoparticles exhibited noteworthy capture efficiency coupled with minimal cytotoxic effects. The assessment of PD-L1 expression consistency between CTCs and tissue specimens revealed a substantial agreement surpassing 70%. Furthermore, inhibition of PD-L1 yielded a significant elevation in the cytokine TNF- α levels, accompanied by a concomitant reduction in IL-10 levels.

Conclusion: The CTC sorting system devised in this investigation boasts attributes of remarkable specificity and sensitivity. By virtue of PD-L1 expression analysis, it holds the potential to offer instructive implications for tailoring individualized treatments in clinical scenarios.

Introduction: Doxorubicin, a first-line chemotherapeutic agent, often faces resistance in breast cancer subtypes, leading to treatment failure. HSPs (Heat shock proteins), especially HSP90, and their pseudogenes like HSP90AB4P have been implicated in fostering resistance mechanisms by regulating apoptotic and survival pathways in cancer cells. The aim of this study is to investigate how inhibiting HSPs using a novel pyro-salicylic acid derivative (7A) can sensitize doxorubicin-resistant breast cancer cells (MCF-7/ADR) to chemotherapy.

Methods: The potential role of HSP inhibitor with doxorubicin at different concentrations was tested to reveal synergetic and additive effects by combination index (CI) analysis. Cell cycle analysis, apoptosis assays, and gene expression profiling via PCR arrays supported the impact of 7A over MCF-7/ADR cells' molecular pathways.

Results: HSP inhibitor efficiently suppressed doxorubicin resistance over invasive breast ductal carcinoma and has a synergetic effect. The inhibitor decreases HSP90AB4P and small HSPB1 expression efficiently.

Conclusion: Our findings demonstrate that 7A suppresses doxorubicin resistance in MCF-7/ADR cells by reducing the expression of HSP90AB4P and small HSPB1, leading to an increase in apoptosis and cell cycle arrest. The combination of 7A and doxorubicin exhibits a synergistic effect (CI < 1), enhancing cytotoxicity and overcoming resistance mechanisms. The cells are driven to apoptosis and the inhibitor significantly decreases doxorubicin resistance. Targeting HSPB1 and its pseudogene HSP90AB4P with 7A offers a promising therapeutic strategy to overcome doxorubicin resistance in breast cancer.

Breast cancer is one of the most common malignancies affecting women worldwide. It is a complex, heterogeneous disease, classified into several subtypes, including hormone receptor-positive and triple-negative breast cancer (TNBC), each with distinct therapeutic challenges. TNBC, in particular, is characterized by its aggressive nature and lack of targeted therapies due to the absence of estrogen, progesterone, and HER2 receptors. This review explores the potential of natural plant-based compounds, especially focusing on Clove Basil (Ocimum sanctum) and Phanera variegata, in combating breast cancer. These plants have been traditionally used for their medicinal properties and are now being studied for their anticancer effects. Ocimum sanctum has demonstrated significant antiproliferative and pro-apoptotic effects against breast cancer cells, particularly the MCF-7 line, through mitochondrial pathway activation and gene regulation. Similarly, Phanera variegata exhibits potential through its rich content of flavonoids and other bioactive compounds, which have been shown to induce apoptosis, reduce tumor growth, and offer antioxidant benefits. The review highlights how these plant extracts, with their multiple mechanisms, including immune modulation and direct cytotoxic effects, hold promise as adjunctive or alternative therapies in breast cancer treatment, particularly for hard-to-treat subtypes like TNBC. Continued research into their molecular pathways and therapeutic efficacy could lead to new, less toxic treatment options.

Introduction: Heterocyclic compounds serve as the structural framework for many commercially available drugs and are well known for their antitumor properties.

Aim: This study aimed to evaluate the cytotoxic effects, apoptosis induction, changes in cell cycle progression, and gene expression alterations of new heterocyclic compounds and their precursors against the acute monocytic leukemia cell line THP-1 through in vitro experimentation and computational approaches.

Methods: The study employed cytotoxicity assays, flow cytometry analyses, gene expression evaluations, oral bioavailability studies, and molecular modeling. Among the compounds tested, 6, 25, and 26 demonstrated the greatest potency and selectivity, exhibiting substantially increased cytotoxicity (1.18 μM < IC50 < 7.66 μM) against the THP-1 cell line. Investigations into apoptosis induction and cell cycle changes revealed that these compounds primarily caused an increase in the number of THP-1 cells undergoing apoptosis after 48 hours of treatment. Additionally, compounds 6 and 25 induced an accumulation of cells in the G0/G1 phase in the same cell line.

Results: Regarding gene expression, a shift in the expression profile of genes associated with apoptotic mechanisms was observed. Furthermore, in silico analysis revealed that these three active compounds potentially interact with histone deacetylase 8 (HDAC8), a protein known to be associated with cancer.

Conclusion: These findings underscore the potential of these compounds as candidates for the development of novel therapeutic approaches in oncology.

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene mutation is commonly found in colorectal, lung, and pancreatic carcinomas. Unfortunately, blocking KRAS straight away has proven to be challenging. PROTACs (Proteolysis Targeting Chimeras), a class of bifunctional molecules, are designed to break down proteins, offering a unique strategy to target KRAS and overcome the limitations of traditional inhibition. This review discusses PROTACs targeting KRAS mutations in cancer, highlighting major findings, current limitations, and future perspectives. To achieve this, we thoroughly analyzed literature sourced from reputable databases, including PubMed, Google Scholar, and ScienceDirect. Various relevant articles were obtained from the reference section of the selected papers. PROTACs successfully induce the degradation of mutant KRAS in cell lines, leading to a decrease in cell viability compared to control groups. PROTAC treatment results in the suppression of downstream signalling pathways associated with KRAS, such as the MAPK and PI3K/AKT pathways. Animal studies demonstrate the ability of the PROTAC to effectively target KRAS-mutant tumors, inhibiting tumour growth without significant toxicities. New advances in this field can lead to cancer treatments that specifically target KRAS-mutant tumors.