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Targeting carbohydrate metabolism in colorectal cancer - synergy between DNA-damaging agents, cannabinoids, and intermittent serum starvation. 针对结直肠癌的碳水化合物代谢--DNA 损伤剂、大麻素和间歇性血清饥饿之间的协同作用。
Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.611
Viktoriia Cherkasova, Olga Kovalchuk, Igor Kovalchuk

Chemotherapy is a therapy of choice for many cancers. However, it is often inefficient for long-term patient survival and is usually accompanied by multiple adverse effects. The adverse effects are mainly associated with toxicity to normal cells, frequently resulting in immune system depression, nausea, loss of appetite and metabolic changes. In this respect, the combination of chemotherapy with cannabinoids, especially non-psychoactive, such as cannabidiol, cannabinol and other minor cannabinoids, as well as terpenes, may become very useful. This is especially pertinent because the mechanisms of anticancer effects of cannabinoids on cancer cells are often different from conventional chemotherapeutics. In addition, cannabinoids help alleviate chemotherapy-induced adverse effects, regulate sleep and appetite, and are shown to have analgesic properties. Another component for achieving potential anti-cancer synergism is regulating nutrient availability and metabolism by calorie restriction and intermittent fasting in cancer cells. As tumours require a lot of energy to grow and because glucose is constantly available, malignant cells often opt to use glucose as a primary source of ATP production through substrate-level phosphorylation (fermentation) rather than through oxidative phosphorylation. Thus, periodic depletion of cancer cells of primary fuel, glucose, could result in a strong synergy in killing cancer cells by chemo- and possibly radiotherapy when combined with cannabinoids. This commentary will discuss what is known about such combinatorial treatments, including potential mechanisms and future protocols.

化疗是许多癌症的首选疗法。然而,化疗对病人的长期存活率往往不高,而且通常伴有多种不良反应。这些不良反应主要与对正常细胞的毒性有关,经常导致免疫系统抑制、恶心、食欲不振和新陈代谢改变。在这方面,化疗与大麻素(尤其是非精神活性的大麻素,如大麻二酚、大麻酚和其他次要大麻素以及萜类化合物)的结合可能非常有用。这一点尤为重要,因为大麻素对癌细胞的抗癌作用机制通常不同于传统的化疗药物。此外,大麻素还有助于减轻化疗引起的不良反应,调节睡眠和食欲,并具有镇痛作用。实现潜在抗癌协同作用的另一个要素是通过限制热量和间歇性禁食来调节癌细胞的营养供应和新陈代谢。由于肿瘤的生长需要大量的能量,而葡萄糖可以随时获得,因此恶性细胞往往选择通过底物级磷酸化(发酵)而不是氧化磷酸化将葡萄糖作为产生 ATP 的主要来源。因此,周期性地消耗癌细胞的主要燃料--葡萄糖,在与大麻素结合使用时,可能会在化疗和放疗杀死癌细胞方面产生强大的协同作用。这篇评论将讨论有关这种组合疗法的已知信息,包括潜在机制和未来方案。
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引用次数: 0
Complete and long-lasting response to immunotherapy in a stage IV non-small cell lung cancer with brain metastasis. 一名 IV 期非小细胞肺癌脑转移患者对免疫疗法的完全和持久反应。
Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.609
Mafalda Costa, Helena Magalhães

Approximately 20% of lung cancer patients have brain metastasis at diagnosis, which is associated with a worse prognosis and a negative impact on quality of life. The emergence of new systemic treatment options such as immune checkpoint inhibitors (ICI) and targeted therapies changed the prognosis for stage IV lung cancer patients. However, the impact of local and systemic treatment sequencing in patients with stage IV lung cancer and brain metastasis is still unclear. We present the case of a 51-year-old man with stage IV non-small cell lung cancer and brain metastasis at diagnosis who underwent whole brain radiotherapy (WBRT) and achieved intracranial and extracranial complete response after second-line treatment with an ICI. Currently, the patient has an overall survival of 87 months and a progression-free survival of 73 months with an optimal quality of life. We hypothesized that treatment sequencing of WBRT and immunotherapy could explain this unexpected outcome.

约 20% 的肺癌患者在确诊时已出现脑转移,这与预后较差和对生活质量的负面影响有关。免疫检查点抑制剂(ICI)和靶向治疗等新的全身治疗方案的出现改变了 IV 期肺癌患者的预后。然而,局部和全身治疗排序对 IV 期肺癌脑转移患者的影响仍不明确。我们报告了一例 51 岁男性患者的病例,他在确诊时患有 IV 期非小细胞肺癌并有脑转移,接受了全脑放疗(WBRT),并在接受 ICI 二线治疗后获得了颅内和颅外完全缓解。目前,患者的总生存期为 87 个月,无进展生存期为 73 个月,生活质量达到最佳。我们假设,WBRT 和免疫疗法的治疗顺序可以解释这一意想不到的结果。
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引用次数: 0
The challenge of weight gain in hormone receptor-positive breast cancer. 激素受体阳性乳腺癌患者体重增加的挑战。
Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.608
Terrence C Tsou, Avonne Connor, Jennifer Y Sheng
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引用次数: 0
Molecular mechanism of PARP inhibitor resistance. PARP 抑制剂耐药性的分子机制。
Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.610
Yi Huang, Simin Chen, Nan Yao, Shikai Lin, Junyi Zhang, Chengrui Xu, Chenxuan Wu, Guo Chen, Danyang Zhou

Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.

聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)是第一种获批的利用合成致死性的抗癌药物。PARPi 可选择性地杀死存在同源重组修复缺陷(HRD)的癌细胞,因此被广泛用于治疗 BRCA1/2 突变的卵巢癌、乳腺癌、胰腺癌和前列腺癌。目前,包括奥拉帕利(Olaparib)、鲁卡帕利(Rucaparib)、尼拉帕利(Niraparib)和塔拉唑帕利(Talazoparib)在内的四种 PARPi 已被开发出来,大大改善了癌症患者的临床疗效。然而,越来越多的证据表明,出现了所需的或新的耐药性。在本综述中,我们将讨论导致 PARPi 耐药的分子机制,并综述克服 PARPi 耐药的潜在策略。
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引用次数: 0
Functional information offers individualized adaptive cancer therapies. 功能信息可提供个性化的适应性癌症疗法。
Pub Date : 2024-07-19 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.607
R Craig Herndon
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引用次数: 0
Unveiling retrotransposon-derived DNA zip code for myeloma cell internalization. 揭示骨髓瘤细胞内化的逆转录转座子衍生 DNA 邮政编码
Pub Date : 2024-07-13 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.606
Pavan Kumar Puvvula, Anthony Johnson, Leon Bernal-Mizrachi
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引用次数: 0
Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma. 针对炎症因子进行化学预防和癌症拦截,以应对恶性间皮瘤。
Pub Date : 2024-05-23 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.605
Joseph R Testa, Yuwaraj Kadariya, Joseph S Friedberg

Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.

间皮瘤是一种无法治愈的间皮内膜癌症,通常由接触石棉引起。石棉引起的炎症是间皮瘤发病的一个重要诱因,遗传因素也是导致这种进展迅速且难治的恶性肿瘤的一个因素。因此,治疗间皮瘤并预防或降低这种致命疾病的总体发病率迫切需要新的方法。在这一研究视角中,我们回顾了石棉诱导的间皮瘤的化学预防和癌症阻断进展现状。我们讨论了用于这些研究的不同临床前小鼠模型,以及可能成为间皮瘤预防潜在靶点的炎症因子。我们还回顾了利用天然植物化学物质和合成制剂进行的初步研究。此外,还介绍了以前在暴露于石棉的人群中进行的临床化学预防试验的结果以及对未来试验的考虑。
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引用次数: 0
Entering the golden age for antibody-drug conjugates in gynecologic cancer. 进入妇科癌症抗体药物结合的黄金时代。
Pub Date : 2024-05-20 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.604
Michelle Greenman, Blair McNamara, Levent Mutlu, Alessandro D Santin
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引用次数: 0
Role of Erk5 expressed in bone marrow mesenchymal stem cells on bone homeostasis and its potential applications in cancer treatment. 骨髓间充质干细胞中表达的 Erk5 对骨稳态的作用及其在癌症治疗中的潜在应用。
Pub Date : 2024-05-20 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.601
Tetsuhiro Horie, Eiichi Hinoi
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引用次数: 0
Primary hepatic angiosarcoma: Treatment options for a rare tumor. 原发性肝血管肉瘤:罕见肿瘤的治疗方案。
Pub Date : 2024-05-20 eCollection Date: 2024-01-01 DOI: 10.18632/oncoscience.602
Gregory L Guzik, Ankit Mangla
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引用次数: 0
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