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Belling the “cat”: Wnt/β-catenin signaling and its significance in future cancer therapies 唤醒 "猫"：Wnt/β-catenin 信号转导及其在未来癌症疗法中的意义

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-15 DOI: 10.1016/j.bbcan.2024.189195

The WNT/β-catenin is among one of the most extensively studied cellular signaling pathways involved in the initiation and progression of several deadly cancers. It is now understood that the WNT/β-catenin signaling, during tumor progression operates in a very complex fashion beyond the earlier assumed simple WNT ‘On’ or ‘Off’ mode as it recruits numerous WNT ligands, receptors, transcriptional factors and also cross-talks with other signaling molecules including the noncanonical WNT regulators. WNT/β-catenin signaling molecules are often mutated in different cancers which makes them very challenging to inhibit and sometimes ranks them among the undruggable targets. Furthermore, due to the evolutionary conservation of this pathway, inhibiting WNT/β-catenin has caused significant toxicity in normal cells. These challenges are reflected in clinical trial data, where the use of WNT/β-catenin inhibitors as standalone treatments remains limited. In this review, we have highlighted the crucial functional associations of diverse WNT/β-catenin signaling regulators with cancer progression and the phenotypic switching of tumor cells. Next, we have shed light on the roles of WNT/β-catenin signaling in drug resistance, clonal evolution, tumor heterogeneity, and immune evasion. The present review also focuses on various classes of routine and novel WNT/β-catenin therapeutic regimes while addressing the challenges associated with targeting the regulators of this complex pathway. In the light of multiple case studies on WNT/β-catenin inhibitors, we also highlighted the challenges and opportunities for future clinical trial strategies involving these treatments. Additionally, we have proposed strategies for future WNT/β-catenin-based drug discovery trials, emphasizing the potential of combination therapies and AI/ML-driven prediction approaches. Overall, here we showcased the opportunities, possibilities, and potentialities of WNT/β-catenin signaling modulatory therapeutic regimes as promising precision cancer medicines for the future.

WNT/β-catenin 是研究最广泛的细胞信号通路之一，它与多种致命癌症的发生和发展有关。现在人们已经了解到，在肿瘤进展过程中，WNT/β-catenin 信号以一种非常复杂的方式运行，超出了早先假定的简单 WNT "开 "或 "关 "模式，因为它招募了许多 WNT 配体、受体和转录因子，还与包括非经典 WNT 调节因子在内的其他信号分子发生交叉作用。在不同的癌症中，WNT/β-catenin 信号分子经常发生突变，这使得抑制它们非常具有挑战性，有时甚至将它们列为无法抑制的靶点。此外，由于该通路在进化过程中保持不变，抑制 WNT/β-catenin 会对正常细胞造成严重毒性。这些挑战反映在临床试验数据中，WNT/β-catenin抑制剂作为独立疗法的使用仍然有限。在这篇综述中，我们强调了多种 WNT/β-catenin 信号调节因子与癌症进展和肿瘤细胞表型转换的重要功能关联。接着，我们阐明了 WNT/β-catenin 信号在耐药性、克隆进化、肿瘤异质性和免疫逃避中的作用。本综述还重点介绍了各类常规和新型 WNT/β-catenin 治疗方案，同时探讨了靶向这一复杂通路的调节因子所面临的挑战。根据有关 WNT/β-catenin 抑制剂的多个案例研究，我们还强调了涉及这些疗法的未来临床试验策略所面临的挑战和机遇。此外，我们还提出了未来基于 WNT/β-catenin 的药物发现试验策略，强调了联合疗法和人工智能/ML 驱动的预测方法的潜力。总之，我们在此展示了 WNT/β-catenin 信号调节治疗方案作为未来有前途的精准癌症药物的机遇、可能性和潜力。

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引用次数: 0

Perioperative immunotherapy for patients with EGFR mutant non-small cell lung cancer: Unexpected potential benefits 为表皮生长因子受体突变非小细胞肺癌患者提供围手术期免疫疗法：意想不到的潜在益处。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-14 DOI: 10.1016/j.bbcan.2024.189194

Given that immunotherapy has resulted in a significant overall survival (OS) benefit in advanced-stage disease, it is of notable interest to determine the effectiveness of these agents in early-stage non-small cell lung cancer (NSCLC). The potential exists for the immunotherapeutic approach in early-stage NSCLC to mirror the paradigm seen in advanced NSCLC, wherein survival enhancements have notably benefited the majority of patients. However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial. In the limited studies that included patients with EGFR mutation status, we found unexpected, good survival benefits of perioperative immune checkpoint inhibitors (ICIs) in resectable EGFR-positive NSCLC, which is controversial with those in advanced EGFR-mutant NSCLC. It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones. The subclonality of the resistant subclone is pivotal in therapy response, with tyrosine kinase inhibitors (TKIs) selectively controlling EGFR-mutant cell proliferation and “competitive release” potentially explaining lower pathological responses in adjuvant TKIs trials. This review delves into emerging data on perioperative treatment modalities for early-stage EGFR mutant NSCLC, exploring unique mechanisms and predictive biomarkers to guide perioperative management strategies.

鉴于免疫疗法已使晚期疾病患者的总生存期（OS）明显改善，因此确定这些药物对早期非小细胞肺癌（NSCLC）的疗效就显得尤为重要。早期非小细胞肺癌的免疫治疗方法有可能与晚期非小细胞肺癌的治疗模式相同，晚期非小细胞肺癌患者的生存率明显提高，使大多数患者受益。然而，免疫疗法在早期表皮生长因子受体（EGFR）突变型 NSCLC 中的表现还存在争议。在纳入表皮生长因子受体突变患者的有限研究中，我们发现围手术期免疫检查点抑制剂（ICIs）对可切除的表皮生长因子受体阳性 NSCLC 有意想不到的良好生存获益，而这与晚期表皮生长因子受体突变 NSCLC 的获益存在争议。这可能是因为免疫环境在肿瘤进展过程中发生了免疫抑制的转变。在疾病的早期阶段，抗肿瘤免疫反应的激活障碍较少。就表皮生长因子受体突变肿瘤而言，瘤内遗传异质性可产生治疗敏感亚克隆和耐药亚克隆。耐药亚克隆的亚克隆性对治疗反应至关重要，酪氨酸激酶抑制剂（TKIs）可选择性地控制表皮生长因子受体突变细胞的增殖，而 "竞争性释放 "可能是辅助TKIs试验中病理反应较低的原因。本综述深入探讨了早期表皮生长因子受体突变 NSCLC 围手术期治疗模式的新数据，探索了指导围手术期管理策略的独特机制和预测性生物标志物。

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引用次数: 0

Advancements in therapeutic peptides: Shaping the future of cancer treatment 治疗肽的进步：塑造癌症治疗的未来。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-10-14 DOI: 10.1016/j.bbcan.2024.189197

In the evolving landscape of cancer treatment, therapeutic peptides are assuming to play an increasingly vital role. Although the number of peptide drugs available for clinical cancer treatment is currently limited, extensive preclinical research is underway, presenting a promising trajectory for the future. The collaborative efforts of natural anti-cancer peptides (ACPs) and synthetic ACPs, propelled by advancements in molecular biology and peptide chemistry, are steering remarkable progress in this domain. We explores the intricate mechanisms underlying the anti-cancer effects of these peptides. The exploration of innovative strategies, including cancer immunotherapy and advanced drug delivery systems, is likely to contribute to the increasing presenceuse of peptide drugs in clinical cancer care. Furthermore, we delve into the potential implications and challenges associated with this anticipated shift, emphasizing the need for continued research and development to unlock the full therapeutic potential of peptide drugs in cancer treatment.

在不断发展的癌症治疗领域，治疗肽正发挥着越来越重要的作用。虽然目前可用于临床癌症治疗的多肽药物数量有限，但广泛的临床前研究正在进行中，为未来的发展提供了良好的前景。在分子生物学和多肽化学进步的推动下，天然抗癌多肽（ACPs）和合成抗癌多肽的共同努力正在这一领域取得显著进展。我们探索了这些肽抗癌作用的复杂机制。对包括癌症免疫疗法和先进给药系统在内的创新策略的探索，很可能会促进肽类药物在临床癌症治疗中的应用。此外，我们还深入探讨了与这一预期转变相关的潜在影响和挑战，强调有必要继续进行研究和开发，以充分释放多肽药物在癌症治疗中的治疗潜力。

引用次数: 0

Comprehensive insights into human papillomavirus and cervical cancer: Pathophysiology, screening, and vaccination strategies 人类乳头瘤病毒与宫颈癌的全面认识：病理生理学、筛查和疫苗接种策略。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-29 DOI: 10.1016/j.bbcan.2024.189192

This article provides an in-depth review of the Human Papillomavirus (HPV), a predominant etiological factor in cervical cancer, exploring its pathophysiology, epidemiology, and mechanisms of oncogenesis. We examine the role of proteins, DNA methylation markers, and non-coding RNAs as predictive biomarkers in cervical cancer, highlighting their potential in refining diagnostic and prognostic practices. The evolution and efficacy of cervical cancer screening methods, including the Papanicolaou smear, HPV testing, cytology and HPV test, and colposcopy techniques, are critically analyzed. Furthermore, the article delves into the current landscape and future prospects of prophylactic HPV vaccines and therapeutic vaccines, underscoring their significance in the prevention and potential treatment of HPV-related diseases. This comprehensive review aims to synthesize recent advances and ongoing challenges in the field, providing a foundation for future research and clinical strategies in the prevention and management of cervical cancer.

本文深入综述了宫颈癌的主要致病因素--人类乳头瘤病毒（HPV），探讨了其病理生理学、流行病学和致癌机制。我们研究了蛋白质、DNA 甲基化标记和非编码 RNA 作为宫颈癌预测性生物标记物的作用，强调了它们在完善诊断和预后实践方面的潜力。文章批判性地分析了宫颈癌筛查方法的演变和功效，包括巴氏涂片、人乳头瘤病毒检测、细胞学和人乳头瘤病毒检测以及阴道镜检查技术。此外，文章还深入探讨了预防性 HPV 疫苗和治疗性疫苗的现状和未来前景，强调了它们在预防和潜在治疗 HPV 相关疾病方面的重要意义。这篇综合评论旨在总结该领域的最新进展和当前挑战，为宫颈癌预防和管理的未来研究和临床策略奠定基础。

引用次数: 0

Roles of miRNAs in regulating ovarian cancer stemness miRNA 在调节卵巢癌干性中的作用

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-29 DOI: 10.1016/j.bbcan.2024.189191

Ovarian cancer is one of the gynaecology malignancies with the highest mortality rate. Ovarian cancer stem cell (CSC) is a subpopulation of ovarian cancer cells with increased self-renewability, aggression, metastatic potentials, and resistance to conventional anti-cancer therapy. The emergence of ovarian CSC is a critical factor that promotes treatment resistance and frequent relapse among ovarian cancer patients, leading to poor clinical outcomes. MicroRNA (miRNA) is a short, non-protein-coding RNA that regulates ovarian CSC development. Although multiple original research articles have discussed the CSC-regulatory roles of different miRNAs in ovarian cancer, there is a deficiency of a review article that can summarize the findings from different research papers. To narrow the gap in the literature, this review aimed to provide an up-to-date summary of the CSC-regulatory roles of various miRNAs in modulating ovarian cancer cell stemness. This review will begin by giving an overview of ovarian CSC and the pathways responsible for driving its appearance. Next, the CSC-regulatory roles of miRNAs in controlling ovarian CSC development will be discussed. Overall, more than 60 miRNAs have been reported to play CSC-regulatory roles in the development and progression of ovarian cancer. By targeting various downstream targets, these miRNAs can control the signaling activities of PI3K/AKT, EGFR/ERK, WNT/ß-catenin, NF-kß, Notch, Hippo/YAP, EMT, and DNA repair pathways. Hence, these CSC-modulatory miRNAs have the potential to be used as prognostic biomarkers in predicting the clinical outcomes of ovarian cancer patients. Targeting CSC-promoting miRNAs or increasing the expressions of CSC-repressing miRNAs can help slow ovarian cancer progression. However, more in-depth functional and clinical trials must be carried out to evaluate the suitability, safety, sensitivity, and specificity of these CSC-regulating miRNAs as prognostic biomarkers or therapeutic targets.

卵巢癌是死亡率最高的妇科恶性肿瘤之一。卵巢癌干细胞（CSC）是卵巢癌细胞的一个亚群，具有更强的自我更新能力、侵袭性、转移潜力和对传统抗癌疗法的抵抗力。卵巢癌干细胞的出现是导致卵巢癌患者耐药和频繁复发的关键因素，从而导致不良的临床预后。微小RNA（miRNA）是一种短小的非蛋白编码RNA，可调控卵巢CSC的发展。虽然已有多篇原创研究文章讨论了不同 miRNA 在卵巢癌中的 CSC 调控作用，但目前还缺少一篇综述文章来总结不同研究论文的发现。为了缩小文献空白，本综述旨在对各种 miRNA 在调节卵巢癌细胞干性中的 CSC 调节作用进行最新总结。本综述将首先概述卵巢干细胞及其出现的驱动途径。接下来，将讨论 miRNA 在控制卵巢 CSC 发展中的 CSC 调节作用。据报道，共有 60 多种 miRNA 在卵巢癌的发生和发展过程中发挥着 CSC 调节作用。通过靶向各种下游靶点，这些miRNA可控制PI3K/AKT、EGFR/ERK、WNT/ß-catenin、NF-kß、Notch、Hippo/YAP、EMT和DNA修复通路的信号活性。因此，这些可调节造血干细胞的 miRNA 有可能被用作预测卵巢癌患者临床结局的预后生物标志物。靶向促进 CSC 的 miRNAs 或增加抑制 CSC 的 miRNAs 的表达有助于减缓卵巢癌的进展。然而，要评估这些调节 CSC 的 miRNA 作为预后生物标志物或治疗靶点的适宜性、安全性、敏感性和特异性，还必须进行更深入的功能和临床试验。

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引用次数: 0

The tumor microenvironment's gambit: Exosomal pawns on the board of head and neck cancer 肿瘤微环境的赌局：头颈癌棋盘上的外泌体棋子

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-27 DOI: 10.1016/j.bbcan.2024.189189

The tumor microenvironment (TME) harbors a hidden universe of interactions that profoundly shape the behavior of head and neck cancers (HNCs). HNCs are not merely localized afflictions; they constitute a pressing global health crisis that impacts millions, frequently resulting in severe prognoses due to late-stage diagnosis and intrinsic resistance to conventional therapies. In this intricate interplay, cancer cells function as strategic players, adeptly manipulating their microenvironment to foster proliferation, evade immune detection, and withstand therapeutic interventions. Central to this dynamic play are exosomes, the enigmatic pawns of cellular communication, carrying vital messages across the board. This review elucidates the multifaceted roles of exosomes within the TME, highlighting their capacity to transmit critical signals that not only promote tumor progression but also modulate immune responses, ultimately playing a crucial role in the evolving narrative of HNC. Our insights aim to catalyze further research and exploration into exosome-targeted therapies, potentially transforming the landscape of HNC treatment and improving clinical outcomes in this formidable battle against cancer.

肿瘤微环境（TME）隐藏着各种相互作用，深刻影响着头颈部癌症（HNCs）的行为。HNCs 不仅仅是局部性疾病，它们还构成了影响数百万人的紧迫的全球健康危机，由于晚期诊断和对传统疗法的内在抵抗力，常常导致严重的预后。在这种错综复杂的相互作用中，癌细胞作为战略参与者，善于操纵其微环境以促进增殖、逃避免疫检测并抵御治疗干预。外泌体是这一动态游戏的核心，它是细胞通信的神秘棋子，全面传递着重要信息。这篇综述阐明了外泌体在TME中的多方面作用，强调了它们传递关键信号的能力，这些信号不仅能促进肿瘤进展，还能调节免疫反应，最终在不断演变的HNC叙述中发挥关键作用。我们的见解旨在促进对外泌体靶向疗法的进一步研究和探索，从而有可能改变 HNC 治疗的格局，改善这场艰巨的抗癌战役的临床结果。

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引用次数: 0

The metabolic crosstalk of cancer-associated fibroblasts and tumor cells: Recent advances and future perspectives 癌症相关成纤维细胞和肿瘤细胞的代谢串扰：最新进展与未来展望

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-26 DOI: 10.1016/j.bbcan.2024.189190

Tumor cells grow in a microenvironment with a lack of nutrients and oxygen. Cancer-associated fibroblasts (CAFs) as one major component of tumor microenvironment have strong ability to survive under stressful conditions through metabolic remodelling. Furthermore, CAFs are educated by tumor cells and help them adapt to the hostile microenvironment through their metabolic communication. By inducing catabolism, CAFs release nutrients into the microenvironment which are taken up by tumor cells to satisfy their metabolic requirements. Furthermore, CAFs can recycle toxic metabolic wastes produced by cancer cells into energetic substances, allowing cancer cells to undergo biosynthesis. Their metabolic crosstalk also enhances CAFs' pro-tumor phenotype and reshape the microenvironment facilitating tumor cells' metastasis and immune escape. In this review, we have analyzed the effect and mechanisms of metabolic crosstalk between tumor cells and CAFs. We also analyzed the future perspectives in this area from the points of CAFs heterogeneity, spatial metabonomics and patient-derived tumor organoids (PDOs). These information may deepen the knowledge of tumor metabolism regulated by CAFs and provide novel insights into the development of metabolism-based anti-cancer strategies.

肿瘤细胞在缺乏营养和氧气的微环境中生长。癌症相关成纤维细胞（CAFs）是肿瘤微环境的主要组成部分之一，它们通过新陈代谢重塑，具有在压力条件下生存的强大能力。此外，CAFs 还接受肿瘤细胞的教育，并通过其代谢交流帮助肿瘤细胞适应恶劣的微环境。通过诱导分解代谢，CAFs 向微环境释放营养物质，肿瘤细胞吸收这些营养物质以满足其代谢需求。此外，CAFs 还能将癌细胞产生的有毒代谢废物回收为能量物质，使癌细胞进行生物合成。它们之间的代谢串联也增强了 CAFs 的亲肿瘤表型，并重塑了有利于肿瘤细胞转移和免疫逃逸的微环境。在这篇综述中，我们分析了肿瘤细胞和 CAFs 之间代谢串扰的影响和机制。我们还从 CAFs 异质性、空间代谢组学和患者衍生肿瘤器官组织（PDOs）等角度分析了这一领域的未来前景。这些信息可能会加深人们对 CAFs 调控肿瘤代谢的认识，并为开发基于代谢的抗癌策略提供新的见解。

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引用次数: 0

Combination therapies with Wnt signaling inhibition: A better choice for prostate cancer treatment 抑制 Wnt 信号的联合疗法：前列腺癌治疗的更佳选择

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-25 DOI: 10.1016/j.bbcan.2024.189186

The intractability and high mortality rate of castration-resistant prostate cancer (CRPC) remain the most challenging problems in the field of prostate cancer (PCa). Emerging evidence has shown that the dysregulation of Wnt signaling pathways, which are highly conserved cascades that regulate embryonic development and maintain tissue homeostasis, is involved in various stages of PCa occurrence and progression. In this review, we systemically discuss the mechanisms by which the androgen receptor (AR) signaling pathway and Wnt signaling pathways participate in the occurrence of PCa and its progression to CRPC. Specifically, we elaborate on how Wnt signaling pathways induce the malignant transformation of prostate cells, promote the malignant progression of PCa and establish an immunosuppressive prostate tumor microenvironment through interaction with the AR pathway or in an AR-independent manner. We also discuss how Wnt signaling pathways enhances the stemness characteristics of prostate cancer stem cells (PCSCs) to induce the occurrence and metastasis of CPPC. Additionally, we discuss the latest progress in the use of different types of drugs that inhibit the Wnt signaling pathways in the treatment of PCa. We believe that the combination of Wnt signaling-based drugs with endocrine and other therapies is necessary and may enhance the clinical efficacy in the treatment of all types of PCa.

难治性和高死亡率仍然是前列腺癌（PCa）领域最具挑战性的问题。新的证据表明，Wnt 信号通路是高度保守的级联，可调节胚胎发育并维持组织稳态，其失调参与了 PCa 发生和发展的各个阶段。在这篇综述中，我们系统地讨论了雄激素受体（AR）信号通路和 Wnt 信号通路参与 PCa 发生和发展为 CRPC 的机制。具体而言，我们阐述了 Wnt 信号通路如何通过与 AR 信号通路相互作用或与 AR 无关的方式诱导前列腺细胞恶性转化、促进 PCa 恶性进展并建立免疫抑制性前列腺肿瘤微环境。我们还讨论了 Wnt 信号通路如何增强前列腺癌干细胞（PCSCs）的干性特征，从而诱导 CPPC 的发生和转移。此外，我们还讨论了使用不同类型的药物抑制 Wnt 信号通路治疗 PCa 的最新进展。我们认为，将基于 Wnt 信号通路的药物与内分泌疗法和其他疗法相结合是必要的，而且可以提高治疗各种类型 PCa 的临床疗效。

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引用次数: 0

Targeting DNA damage response in pancreatic ductal adenocarcinoma: A review of preclinical and clinical evidence 针对胰腺导管腺癌的 DNA 损伤反应：临床前和临床证据综述。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-24 DOI: 10.1016/j.bbcan.2024.189185

Pancreatic ductal adenocarcinoma (PDAC) is associated with one of the most unfavorable prognoses across all malignancies. In this review, we investigate the role of inhibitors targeting crucial regulators of DNA damage response (DDR) pathways, either as single treatments or in combination with chemotherapeutic agents and targeted therapies in PDAC. The most prominent clinical benefit of PARP inhibitors' monotherapy is related to the principle of synthetic lethality in individuals harboring BRCA1/2 and other DDR gene mutations as predictive biomarkers. Moreover, induction of BRCAness with inhibitors of RTKs, including VEGFR and c-MET and their downstream signaling pathways, RAS/RAF/MEK/ERK and PI3K/AKT/mTOR in order to expand the application of PARP inhibitors in patients without DDR mutations, has also been addressed. Other DDR-targeting agents beyond PARP inhibitors, including inhibitors of ATM, ATR, CHEK1/2, and WEE1 have also demonstrated their potential in preclinical models of PDAC and may hold promise in future studies.

胰腺导管腺癌（PDAC）是所有恶性肿瘤中预后最差的一种。在这篇综述中，我们研究了针对 DNA 损伤应答（DDR）通路关键调控因子的抑制剂在 PDAC 中作为单一疗法或与化疗药物和靶向疗法联合使用所发挥的作用。PARP抑制剂单药治疗最突出的临床疗效与作为预测性生物标志物的BRCA1/2和其他DDR基因突变个体的合成致死原则有关。此外，为了扩大 PARP 抑制剂在无 DDR 基因突变患者中的应用，还研究了用 RTK 抑制剂诱导 BRCAness，包括 VEGFR 和 c-MET 及其下游信号通路 RAS/RAF/MEK/ERK 和 PI3K/AKT/mTOR。PARP 抑制剂之外的其他 DDR 靶向药物，包括 ATM、ATR、CHEK1/2 和 WEE1 的抑制剂，也已在 PDAC 的临床前模型中证明了其潜力，并可能在未来的研究中大有可为。

引用次数: 0

Intercellular adhesion molecule-1 (ICAM-1): From molecular functions to clinical applications in cancer investigation 细胞间粘附分子-1 (ICAM-1)：从分子功能到癌症研究中的临床应用

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2024-09-22 DOI: 10.1016/j.bbcan.2024.189187

Intercellular adhesion molecule-1 (ICAM-1) is a versatile molecule that plays a critical role in various physiological and pathological processes, particularly in tumor development where its impact is bidirectional. On the one hand, it augments the immune response by promoting immune cell migration, infiltration, and the formation of immunological synapses, thus facilitating potent antitumor effects. Simultaneously, it contributes to tumor immune evasion and influences metastasis by mediating transendothelial migration (TEM), epithelial-to-mesenchymal transition (EMT), and epigenetic modification of tumor cells. Despite its significant potential, the full clinical utility of ICAM-1 has yet to be fully realized. In this review, we thoroughly examine recent advancements in understanding the role of ICAM-1 in tumor development, its relevance in predicting therapeutic efficacy and prognosis, as well as the progress in clinical translational research on anti-ICAM-1-based therapies, encompassing including monoclonal antibodies, immunotherapy, antibody-drug conjugate (ADC), and conventional treatments. By shedding light on these innovative strategies, we aim to underscore ICAM-1's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.

细胞间粘附分子-1（ICAM-1）是一种多功能分子，在各种生理和病理过程中发挥着关键作用，尤其是在肿瘤发生发展过程中，它的影响是双向的。一方面，它通过促进免疫细胞迁移、浸润和免疫突触的形成来增强免疫反应，从而促进有效的抗肿瘤作用。同时，它还通过介导肿瘤细胞的跨内皮迁移（TEM）、上皮细胞向间质转化（EMT）和表观遗传学改变，促进肿瘤免疫逃避并影响肿瘤转移。尽管 ICAM-1 具有巨大的潜力，但其临床用途尚未得到充分发挥。在这篇综述中，我们将深入探讨最近在了解 ICAM-1 在肿瘤发生发展中的作用、其在预测疗效和预后方面的相关性以及基于抗 ICAM-1 疗法的临床转化研究进展方面取得的进展，包括单克隆抗体、免疫疗法、抗体药物结合物 (ADC) 和传统疗法。通过揭示这些创新策略，我们旨在强调 ICAM-1 作为癌症治疗的一个有价值的、多方面的靶点的意义，点燃进一步研究的热情，促进转化为临床应用。

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引用次数: 0