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Rationale for the Use of Homologous Recombination Proficient Molecular Profile as a Biomarker for Therapeutic Targeting in Ovarian Cancer. 使用同源重组高效分子图谱作为癌症靶向治疗的生物标志物的基本原理。
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-09-20 eCollection Date: 2023-01-01 DOI: 10.3389/or.2023.11471
John Nemunaitis, Laura Stanbery, Adam Walter, Rodney Rocconi, Philip Stephens
Therapeutic options for advanced-stage ovarian cancer patients are limited in those subjects with homologous recombination proficient molecular profiles. A recent review of the existing literature demonstrates evidence of enhanced relapse-free survival and overall survival associated with treatment with Vigil in the Phase 2b trial in the HRP population. Homologous recombination (HR) is a genetic rearrangement in which molecular information is exchanged between two similar molecules of double-stranded or single-stranded nucleic acids [1]. The purpose of HR is to maintain genome stability by performing high-fidelity repair of complex DNA damage such as DNA doublestrand breaks and interstrand crosslinks [2–4]. Homologous recombination is responsible for double-stranded DNA breaks and interstrand crosslink damage repair through the use of sister chromatids as a repair template. BRCA1/2 are critically important proteins in this pathway. HR deficiency (D) is the result of germline or somatic genetic alterations in HR genes (i.e., BRCA 1 or 2) [5]. Dysfunctional HR genes cause genome-wide errors and can lead to tumorigenesis [6, 7]. Tumors that are not HRD are considered HR proficient (P) and contain no functional genetic alterations in HR pathway genes, like BRCA1/2, resulting in faithful DNA repair, thereby reducing the mutation burden. While the HR pathway is responsible for repairing double-stranded breaks, the base excision repair pathway repairs single-stranded DNA breaks. Poly (ADP-ribose) polymerase proteins (PARPs) are essential proteins in this pathway. When PARPs are inhibited, single-stranded breaks are converted to double-stranded breaks during DNA replication. Synthetic lethality occurs in cells treated with a PARP inhibitor that have a BRCAmutation or are HRD. Alterations in HR pathway genes, especially mutations in BRCA1/2, can be germline and confer familial risk for breast, ovarian, prostate, and pancreatic cancer [8] or somatic. For patients who demonstrate negative germline testing, somatic HR molecular status is assessed by NGS and is most commonly evaluated by Myriad’s MyChoice CDx-testing. This involves the analysis of BRCA 1 and 2 gene mutation status, loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and largescale state transition score (LST) to determine a genomic instability score (GIS) [9]. Each is weighted and scored using a proprietary algorithm to determine the level of genomic instability. A GIS ≥42 in BRCA 1 or 2 negative patients defines HRD status. A GIS score <42 defines HRP status [10]. BRCA 1 or 2 mutations or HRDmolecular profile tumors are a sensitive ovarian cancer population to PARP inhibitor therapy [10–14] and are associated with a better prognosis in patients receiving platinumbased chemotherapy and/or bevacizumab [15]. However, ovarian cancer patients with HRP molecular status have a worse prognosis with standard-of-care therapy involving PARPIs, Edited by: Angela Cappello, University of Rome
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引用次数: 1
Timing of Early Salvage Therapy for Patients With Biochemical Relapse of Prostate Carcinoma. 前列腺癌生化复发患者早期挽救治疗的时机。
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-09-13 eCollection Date: 2023-01-01 DOI: 10.3389/or.2023.10676
Soňa Argalácsová, Michal Vočka, Otakar Čapoun, Lukáš Lambert

Between 25% and 33% of patients after radical prostatectomy experience a relapse of the disease. The risk of relapse increases in patients with risk factors up to 50%-80%. For a long time, adjuvant radiotherapy has been considered the standard of care. Four large prospective trials, that compared adjuvant and salvage radiotherapy in patients with biochemical relapse, showed the superiority of the adjuvant approach in biochemical and local relapse-free survival, but no consistent benefit in long-term endpoints (i.e., metastasis-free survival, overall survival, or carcinoma-specific survival) at the expense of increased urinary and bowel toxicity. Three large international studies comparing adjuvant and salvage radiotherapy paved the way toward early salvage radiotherapy. However, the optimal threshold of the PSA level (range of 0.2-0.5 ng/mL) for initiating early salvage radiotherapy remains unresolved and still poses a challenge in everyday clinical practice when balancing the need for early radiotherapy and the associated toxicity. Imprecise stratification of biochemical relaps patients according to the risk of clinical relapse drives efforts to find additional molecular biomarkers that would improve the timing of the salvage therapy.

根治性前列腺切除术后,25%至33%的患者会复发。风险因素高达50%-80%的患者复发风险增加。长期以来,辅助放射治疗一直被认为是治疗的标准。四项大型前瞻性试验比较了生物化学复发患者的辅助和挽救性放疗,显示了辅助方法在生物化学和局部无复发生存率方面的优越性,但在长期终点(即无转移生存率、总生存率或癌症特异性生存率)方面没有以增加尿和肠毒性为代价的一致益处。三项比较辅助放疗和挽救性放疗的大型国际研究为早期挽救性放疗铺平了道路。然而,启动早期挽救性放射治疗的PSA水平的最佳阈值(范围为0.2-0.5ng/mL)仍未解决,并且在平衡早期放射治疗的需求和相关毒性时,在日常临床实践中仍然存在挑战。根据临床复发风险对生化相关性患者进行不精确的分层,促使人们努力寻找额外的分子生物标志物,以改善挽救治疗的时机。
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引用次数: 0
Cancer—A Pragmatic Switch to Combat Metabolic Syndrome? 癌症——对抗代谢综合征的务实转变?
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-02-15 DOI: 10.3389/or.2023.10573
John A. Claras
Both cancer and metabolic disease have become the prevalent health risks in modern societies worldwide. Cancer is a complex set of illnesses with many definitions. About 15% of cancers are caused by infections, and 10% carry a hereditary burden. The remaining 70%–75% cancers are associated with a variety of processes, often associated with metabolic syndrome and chronic inflammation. This review examines the role of metabolic dysfunction and chronic inflammation in cancer development. I propose a novel concept of a switch, in which our intelligent body uses its sophisticated set of subsystems and sensors to pragmatically anticipate and combat metabolic dysfunction as its’ most direct and dire threat first, while temporarily accepting cancer as a state that in any other circumstances would be considered detrimental, and utilizing cancer as an additional tool to lower glucose levels. Once metabolic dysfunction has been resolved this switch is reversed, and cancer growth will be impaired.
癌症和代谢性疾病已成为当今世界普遍存在的健康风险。癌症是一组复杂的疾病,有很多定义。大约15%的癌症是由感染引起的,10%的癌症带有遗传负担。其余70%-75%的癌症与多种过程有关,通常与代谢综合征和慢性炎症有关。本文综述了代谢功能障碍和慢性炎症在癌症发展中的作用。我提出了一个新的开关概念,在这个概念中,我们的智能身体首先使用其复杂的子系统和传感器,务实地预测和对抗代谢功能障碍,将其作为“最直接和最可怕的威胁”,同时暂时接受癌症作为一种状态,在任何其他情况下都被认为是有害的,并利用癌症作为降低血糖水平的额外工具。一旦代谢功能障碍得到解决,这种转换就会被逆转,癌症的生长就会受到损害。
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引用次数: 0
Rosetta Stone for Cancer Cure: Comparison of the Anticancer Capacity of Endogenous Estrogens, Synthetic Estrogens and Antiestrogens. 癌症治疗的罗塞塔石碑:内源性雌激素、合成雌激素和抗雌激素抗癌能力的比较。
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-01-01 DOI: 10.3389/or.2023.10708
Zsuzsanna Suba

This work presents the history of the recognition of principal regulatory capacities of estrogen hormones having been mistakenly regarded as breast cancer promoting agents for more than 120 years. Comprehensive analysis of the results of clinical, epidemiological, immunological and molecular studies justified that endogenous estrogens are the principal regulators of embryonic development, survival and reproduction via orchestrating appropriate expression and even edition of all genes in mammalians. Medical use of chemically modified synthetic estrogens caused toxic complications; thromboembolic events and increased cancer risk in female organs as they proved to be endocrine disruptors deregulating estrogen receptors (ERs) rather than their activators. Synthetic estrogen treatment exhibits ambiguous correlations with cancer risk at different sites, which may be attributed to an inhibition of the unliganded activation of estrogen receptors (ERs) coupled with compensatory liganded activation. The principle of estrogen induced breast cancer led to the introduction of antiestrogen therapies against this tumor; inhibition of the liganded activation of estrogen receptors and aromatase enzyme activity. The initial enthusiasm turned into disappointment as the majority of breast cancers proved to be primarily resistant to antiestrogens. In addition, nearly all patients showing earlier good tumor responses to endocrine therapy, later experienced secondary resistance leading to metastatic disease and fatal outcome. Studying the molecular events in tumors responsive and unresponsive to antiestrogen therapy, it was illuminated that a complete inhibition of liganded ER activation stimulates the growth of cancers, while a successful compensatory upregulation of estrogen signal may achieve DNA restoration, tumor regression and patient's survival. Recognition of the principal role of endogenous estrogens in gene expression, gene edition and DNA repair, estrogen treatment and stimulation of ER expression in patients may bring about a great turn in medical practice.

这项工作提出了认识雌激素激素的主要调节能力的历史,被错误地认为是乳腺癌的促进剂超过120年。对临床、流行病学、免疫学和分子研究结果的综合分析证明,内源性雌激素是哺乳动物胚胎发育、生存和繁殖的主要调节剂,通过协调所有基因的适当表达甚至编辑。医学上使用化学修饰的合成雌激素引起毒性并发症;血栓栓塞事件和女性器官癌症风险增加,因为它们被证明是内分泌干扰物,解除了雌激素受体(er)的调节,而不是雌激素受体的激活剂。合成雌激素治疗与不同部位的癌症风险表现出模糊的相关性,这可能归因于抑制雌激素受体(er)的非配体激活以及代偿配体激活。雌激素诱发乳腺癌的原理导致了针对这种肿瘤的抗雌激素疗法的引入;雌激素受体的配体活化和芳香酶活性的抑制。最初的热情变成了失望,因为大多数乳腺癌被证明主要对抗雌激素有抗药性。此外,几乎所有早期对内分泌治疗表现出良好肿瘤反应的患者,后来都经历了导致转移性疾病和致命结局的继发性耐药。通过对抗雌激素治疗有应答和无应答肿瘤的分子事件的研究,揭示了完全抑制配体内质网的激活可以刺激肿瘤的生长,而成功的补偿性上调雌激素信号可以实现DNA的修复、肿瘤的消退和患者的生存。认识到内源性雌激素在基因表达、基因编辑和DNA修复、雌激素治疗和刺激患者ER表达中的主要作用,可能会给医疗实践带来重大转变。
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引用次数: 0
Changing Colorectal Cancer Trends in Asians: Epidemiology and Risk Factors. 亚洲人结直肠癌趋势的变化:流行病学和危险因素。
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-01-01 DOI: 10.3389/or.2023.10576
Carissa Ikka Pardamean, Digdo Sudigyo, Arif Budiarto, Bharuno Mahesworo, Alam Ahmad Hidayat, James W Baurley, Bens Pardamean

Once an infrequent disease in parts of Asia, the rate of colorectal cancer in recent decades appears to be steadily increasing. Colorectal cancer represents one of the most important causes of cancer mortality worldwide, including in many regions in Asia. Rapid changes in socioeconomic and lifestyle habits have been attributed to the notable increase in the incidence of colorectal cancers in many Asian countries. Through published data from the International Agency for Cancer Research (IARC), we utilized available continuous data to determine which Asian nations had a rise in colorectal cancer rates. We found that East and South East Asian countries had a significant rise in colorectal cancer rates. Subsequently, we summarized here the known genetics and environmental risk factors for colorectal cancer among populations in this region as well as approaches to screening and early detection that have been considered across various countries in the region.

在亚洲部分地区,结直肠癌曾经是一种罕见的疾病,但近几十年来,结直肠癌的发病率似乎在稳步上升。结直肠癌是全世界包括亚洲许多地区癌症死亡的最重要原因之一。社会经济和生活习惯的快速变化是许多亚洲国家结直肠癌发病率显著增加的原因。通过国际癌症研究机构(IARC)公布的数据,我们利用现有的连续数据来确定哪些亚洲国家的结直肠癌发病率上升。我们发现东亚和东南亚国家的结直肠癌发病率显著上升。随后,我们总结了该地区人群中已知的结直肠癌遗传和环境风险因素,以及该地区各国考虑的筛查和早期发现方法。
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引用次数: 1
Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors. 实体肿瘤治疗药物传递的挑战与机遇。
IF 3.6 Q2 ONCOLOGY Pub Date : 2023-01-01 DOI: 10.3389/or.2023.10577
Teona Paresishvili, Zurab Kakabadze

In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that demonstrate promising results for the treatment of various types of cancer using metal-based nanoparticles. Due to their unique physical and chemical properties, metal nanoparticles are effectively being used for the delivery of drug to the tumor cells, for cancer diagnosis and treatment. They can also be synthesized allowing the control of size and shape. However, the effectiveness of the metal nanoparticles for cancer treatment largely depends on their stability, biocompatibility, and ability to selectively affect tumor cells after their systemic or local administration. Another major problem associated with metal nanoparticles is their ability to overcome tumor tissue barriers such as atypical blood vessel structure, dense and rigid extracellular matrix, and high pressure of tumor interstitial fluid. The review also describes the design of tumor drug delivery systems that are based on metal nanoparticles. The mechanism of action of metal nanoparticles on cancer cells is also discussed. Considering the therapeutic safety and toxicity of metal nanoparticles, the prospects for their use for future clinical applications are being currently reviewed.

在本文中,我们讨论了基于金属纳米颗粒的药物递送系统的有效性,并描述了与它们递送到肿瘤细胞相关的问题。近年来,文献中出现了更多的报告,证明了使用金属基纳米颗粒治疗各种类型癌症的有希望的结果。由于其独特的物理和化学性质,金属纳米颗粒被有效地用于向肿瘤细胞输送药物,用于癌症的诊断和治疗。它们也可以合成,允许控制大小和形状。然而,金属纳米颗粒治疗癌症的有效性在很大程度上取决于它们的稳定性、生物相容性以及在全身或局部给药后选择性影响肿瘤细胞的能力。与金属纳米颗粒相关的另一个主要问题是它们克服肿瘤组织障碍的能力,如非典型血管结构、致密和坚硬的细胞外基质以及肿瘤间质液的高压。本文还介绍了基于金属纳米颗粒的肿瘤药物传递系统的设计。讨论了金属纳米颗粒对癌细胞的作用机制。考虑到金属纳米颗粒的治疗安全性和毒性,目前正在对其未来临床应用的前景进行综述。
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引用次数: 0
Deciphering Driver of Nasopharyngeal Cancer Development. 破译鼻咽癌发展的驱动因素
IF 3.1 Q2 ONCOLOGY Pub Date : 2022-10-11 eCollection Date: 2022-01-01 DOI: 10.3389/or.2022.10654
Handoko, Melva Louisa, Tiara Bunga Mayang Permata, Soehartati A Gondhowiardjo

A great deal of progress has been made on understanding nasopharyngeal cancer in recent decades. Genomic, transcriptomic, and proteomic studies have enabled us to gain a deeper understanding on the biology of nasopharyngeal cancer, and though this new information is elaborate and detailed, an overall picture of the driver of nasopharyngeal cancer that includes all this information is lacking. This review will focus on providing a broad overview, with plausible and simple language, on nasopharyngeal carcinogenesis based on current updated information. This will help readers to gain a broad understanding, which may be necessary to provide common ground for further research on nasopharyngeal cancer.

近几十年来,人们在了解鼻咽癌方面取得了很大进展。基因组学、转录组学和蛋白质组学研究使我们对鼻咽癌的生物学特性有了更深入的了解,尽管这些新信息详尽而详细,但我们仍缺乏一个包含所有这些信息的鼻咽癌驱动因素的整体图景。本综述将以当前的最新信息为基础,以合理而简洁的语言,重点概述鼻咽癌的致癌因素。这将有助于读者获得广泛的理解,为进一步研究鼻咽癌提供必要的共同基础。
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引用次数: 0
Neoadjuvant Chemotherapy Versus Primary Debulking Surgery in FIGO Stage III and IV Epithelial Ovarian, Tubal or Peritoneal Cancer: A Systematic Review and Meta-Analysis. FIGO III期和IV期上皮性卵巢癌、输卵管癌或腹膜癌的新辅助化疗与原发性减体积手术:系统回顾和荟萃分析
IF 3.6 Q2 ONCOLOGY Pub Date : 2022-09-27 eCollection Date: 2022-01-01 DOI: 10.3389/or.2022.10605
Alexander A Tzanis, Christos Iavazzo, Alexandros Hadjivasilis, Hara Tsouvali, George Α Antoniou, Stavros A Antoniou

Objective: To investigate whether neoadjuvant chemotherapy (NACT) confers superior outcomes compared to primary debulking surgery (PDS) in patients with stage III and IV epithelial ovarian, tubal or peritoneal cancer as well as in patients with high tumour load. Methods: We searched the electronic databases PubMed, Cochrane Central Register of Controlled trials, and Scopus from inception to March 2021. We considered randomised controlled trials (RCTs) comparing NACT with PDS for women with epithelial ovarian cancer (EOC) stages III and IV. The primary outcomes were overall survival and progression-free survival. Secondary outcomes were optimal cytoreduction rates, peri-operative adverse events, and quality of life. Results: Six RCTs with a total of 1901 participants were included. Meta-analysis demonstrated similar overall survival (HR = 0.96, 95% CI [0.86-1.07]) and progression-free survival (HR = 0.98, 95% CI [0.89-1.08]) between NACT and PDS. Subgroup analyses did not demonstrate higher survival for stage IV patients (HR = 0.88, 95% CI [0.71-1.09]) nor for patients with metastatic lesions >5 cm (HR = 0.86, 95% CI [0.69-1.08]) treated with NACT, albeit with some uncertainty due to imprecision. Similarly, no survival benefit was observed in the subgroup of patients with metastatic lesions >10 cm (HR = 0.94, 95% CI [0.78-1.12]). NACT was associated with significantly higher rates of complete cytoreduction (RR = 2.34, 95% CI [1.48-3.71]). Severe peri-operative adverse events were less frequent in the NACT arm (RR = 0.34, 95% CI [0.16-0.72]. Conclusion: Patients with stage III and IV epithelial ovarian cancer undergoing NACT or PDS have similar overall survival. NACT is likely associated with higher rates of complete cytoreduction and lower risk of severe adverse events and peri-operative death.

目的:研究与初次减瘤手术(PDS)相比,新辅助化疗(NACT)在癌症、输卵管癌或腹膜癌III期和IV期患者以及高肿瘤负荷患者中是否具有优越的疗效。方法:从开始到2021年3月,我们搜索了电子数据库PubMed、Cochrane对照试验中央登记册和Scopus。我们考虑了对上皮性卵巢癌症(EOC)III期和IV期妇女进行NACT和PDS比较的随机对照试验(RCT)。主要结果是总生存率和无进展生存率。次要结果是最佳细胞减少率、围手术期不良事件和生活质量。结果:纳入6项随机对照试验,共1901名参与者。荟萃分析显示,NACT和PDS之间的总生存率(HR=0.96,95%CI[0.86-1.07])和无进展生存率(HR=0.98,95%CI[0.89-1.08])相似。亚组分析没有显示接受NACT治疗的IV期患者(HR=0.88,95%CI[0.711-1.09])和转移性病变>5cm(HR=0.86,95%CI[0.69-1.08])的生存率更高,尽管由于不精确性存在一些不确定性。类似地,在转移性病变>10cm的患者亚组中没有观察到生存益处(HR=0.94,95%CI[0.78-1.12])。NACT与显著更高的完全细胞减少率相关(RR=2.34,95%CI[1.48-3.71])。NACT组严重的围手术期不良事件发生率较低(RR=0.34,95%CI[0.16-0.72]结论:接受NACT或PDS治疗的癌症III期和IV期患者的总生存率相似。NACT可能与更高的完全细胞减少率和更低的严重不良事件和围手术期死亡风险有关。
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引用次数: 1
Residential radon exposure and cancer 住宅氡暴露与癌症
IF 3.6 Q2 ONCOLOGY Pub Date : 2022-02-22 DOI: 10.4081/oncol.2022.558
Akhila Reddy, Camila Conde, Christopher Peterson, Kenneth M Nugent
Radon is an established human lung carcinogen naturally released as an odorless, colorless gas from soil and rocks. It is a major environmental source of ionizing radiation and can cause oxidative damage to DNA, increasing the risk of lung cancer. Although the association between radon and lung cancer is well established, the association between radon and other cancers is not. Based on reported studies, there is no consistent evidence indicating an association between radon and non-solid and solid cancers, but limited literature, heterogenous study design, and confounding variables preclude definitive conclusions. More research is needed to evaluate the association between residential radon and non-lung cancers, particularly with regard to skin cancer, central nervous system (CNS) cancer, renal, and stomach cancer, in which existing literature suggests potential associations with residential radon may exist. However, the literature largely demonstrates that lung cancer is the primary concern associated with residential radon exposure; the lack of association with nonlung cancers could reflect the lack of studies which have an adequate sample size, establish accurate levels of radon exposure, and control for confounders. These results should be considered in residential radon mitigation efforts which should focus on smokers with high radon exposures.
氡是一种公认的人类肺部致癌物质,它是从土壤和岩石中自然释放出来的无色无味气体。它是电离辐射的主要环境来源,可对DNA造成氧化损伤,增加患癌症的风险。尽管氡与癌症之间的联系已经确立,但氡与其他癌症之间的联系却不是。根据已报道的研究,没有一致的证据表明氡与非实体癌和实体癌之间存在关联,但有限的文献、异质性研究设计和混杂的变量排除了明确的结论。需要更多的研究来评估住宅氡与非肺癌之间的关系,特别是在皮肤癌症、中枢神经系统癌症、肾脏和癌症方面,现有文献表明可能存在与住宅氡的潜在关联。然而,文献在很大程度上表明,癌症是与住宅氡暴露相关的主要问题;与非肺癌缺乏关联可能反映出缺乏足够的样本量、确定准确的氡暴露水平和控制混杂因素的研究。这些结果应在住宅氡减排工作中加以考虑,重点应放在氡暴露量高的吸烟者身上。
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引用次数: 11
Molecular drivers of oral cavity squamous cell carcinoma in non-smoking and non-drinking patients: what do we know so far? 不吸烟和不饮酒患者口腔鳞状细胞癌的分子驱动因素:我们目前了解多少?
IF 3.1 Q2 ONCOLOGY Pub Date : 2022-02-22 DOI: 10.4081/oncol.2022.549
Sophia Uddin, Alka Singh, Vasudha Mishra, Nishant Agrawal, Zhen Gooi, Evgeny Izumchenko

Oral cavity squamous cell carcinoma (OCSCC) is one of the most common head and neck cancers worldwide. It is well known that risk factors for OCSCC include tobacco and excess alcohol consumption. However, in recent years, OCSCC incidence has been increasing in patients without these traditional risk factors. The cause of this increase is unclear and various genetic, environmental, and infectious factors have been hypothesized to play a role. Additionally, there are expert opinions that oral cancer in non-smoking, non-drinking (NSND) patients have a distinct phenotype resulting in more aggressive disease presentation and poorer prognosis. In this review, we summarize the current state of knowledge for oral cavity cancer in patients without traditional risk factors.

口腔鳞状细胞癌(OCSCC)是全球最常见的头颈部癌症之一。众所周知,OCSCC 的危险因素包括吸烟和过量饮酒。然而,近年来,没有这些传统危险因素的患者的 OCSCC 发病率却在上升。导致发病率上升的原因尚不清楚,各种遗传、环境和感染因素被认为是其中的一个原因。此外,有专家认为,不吸烟、不饮酒(NSND)患者的口腔癌具有独特的表型,其疾病表现更具侵袭性,预后更差。在这篇综述中,我们总结了目前对无传统风险因素患者口腔癌的认识。
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引用次数: 0
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Oncology Reviews
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