Survivin:Potential role in diagnosis,prognosis and targeted therapy of gastric cancer

Survivin is a protein that is highly expressed in a vast number of malignancies,but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells,thus facilitating the growth of these cells. In the case of gastric cancer,survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells,it has been described as an "ideal target" for cancer therapy. Currently,several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis,prognosis and treatment of gastric tumors.

Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy

There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.

Neoadjuvant targeted therapy for apocrine carcinoma of the breast:A case report

BACKGROUND Apocrine carcinoma of the breast is a special type of invasive ductal carcinoma of the breast that is rare in clinical practice.Neoadjuvant therapy,especially neoadjuvant targeted therapy,has rarely been reported for apocrine carcinoma of the breast.CASE SUMMARY A 63-year-old woman presented with apocrine carcinoma of the left breast underwent core needle biopsy.The patient was diagnosed with apocrine carcinoma by immunohistochemical staining and negative hormone status(estrogen receptor and progesterone receptor)but showed overexpression of human epidermal factor receptor 2(HER-2).Moreover,positive expression of androgen receptor(approximately 60%)and gross cystic disease fluid protein 15 was observed.The patient was treated with neoadjuvant targeted therapy consisting of the TCH regimen(docetaxel,carboplatin area under curve 6 and trastuzumab)every 21 d.The mass in the left breast was significantly reduced,and pain in the breast and left upper arm also improved.CONCLUSION HER-2 positive apocrine carcinoma of the breast can be improved by neoadjuvant chemotherapy combined with targeted therapy.

The “predictive molecule targeted chemotherapy” for relapsed ovarian cancer—a pilot study

Objective: How to choose chemotherapy regimen is a often-encountered and formidable problem in the setting of relapsed ovarian cancer. So far, it was usually according to the clinical trials and doctors’ experience and the response rate was very low. In the present study, we proposed a new treatment strategy–the “predictive molecule targeted chemotherapy, PMTC” to choose supposedly sensitive protocols and void supposedly resistant protocols based on the specific predictive molecule expression of individual tumor tissue. Methods: Retrospectively analysis of 16 cases of relapsed ovarian cancer patients from January 2002 to December 2003, as the experience-directed chemotherapy group (control group), to calculate the response rate. Prospectively recruit 9 cases of relapsed ovarian cancer patients after January 2004, whose chemotherapy drug choice was based on the expression of 6 predictive molecules (p53, et al) by means of immunohistochemistry, as the PMTC group, to calculate the response rate. χ2 test was used for the statistical analysis. Results: The response rate of control group was 26%, including 31% for second line and 14% for third line respectively. The response rate of PMTC group was 78%, in which 5 cases of early relapse all responded. The difference was significant (P=0.011). Conclusions: PMTC is a new effective method to treat the relapsed ovarian cancer.

Application of phage display technology in targeted therapy of breast cancer

Phage display is a technology of gene expression and screening, it is widely used in the fields of defining antigen epitopes, signal transduction, genetic treatment, parasites research and tumor targeted therapy. Breast cancer is the most common cancer in women, we can obtain peptides specially associated with breast cancer by using phage display technology, and this method has great potential in early diagnosis of breast cancer and development new targeted drugs.

In vitro effects of monoclonal antibody targeted daunomycin on human gastric cancer cells

In the present study,daunomydn （DIM） was chosen to conjugate cowdently with amonoclonal antitibody,MGb2,against human gastric cancer cells via a cis-aconitic anhydride linker（directly） or a dextmn bridge （indirectly,） The mo-lar ratio of MGb2 to DM in the conjugates was1:6 （direct method） and 1:54 （indirect method）,respectively.The ELISA results revealed theantibody after conjugation retained antigen-binding capacity.The conjugates showed a highly se-lective cytotoxicity to the target cells.In lh cytotoxidty test,cytotoxidty of the conjugates wasgreater than that of free DM or irrevalent conjugates to human gastric cancer cell lines,SGC-7901and very low as far as non-target cells （HeLa） were concerned.It is sugared that theselective cytotoxidty on target cells of the conjugates is mediated by the monoclonal antibody.

Advancing the understanding and management of blastic plasmacytoid dendritic cell neoplasm:Insights from recent case studies

We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.

Molecular targeted therapy of gynecological malignanttumors: the development and challenge, from laboratory toclinic

More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer,especially in ovarian cancer.In this article,we systematically review the current targeted therapeutic trials running in clinic.Large,randomized trials have been conducted in the treatment of ovarian cancer,endometrial cancer and cervical cancer by using small molecule,antisense,mutational gene as well as antibodies.Other planned or ongoing trials currently targeted at molecular markers which may play important roles in gynecological carcinogenesis and progression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an important option.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Targeting head and neck tumoral stem cells： From biologicalaspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

RON in hepatobiliary and pancreatic cancers:Pathogenesis and potential therapeutic targets

The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family.Research has shown that RON has a role in cancer pathogenesis,which places RON on the frontline of the development of novel cancer therapeutic strategies.Hepatobiliary and pancreatic(HBP)cancers have a poor prognosis,being reported as having higher rates of cancer-related death.Therefore,to combat these malignant diseases,the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis,and the development of RON as a drug target for therapeutic intervention should be investigated.Abnormal RON expression and signaling have been identified in HBP cancers,and also act as tumorigenic determinants for HBP cancer malignant behaviors.In addition,RON is emerging as an important mediator of the clinical prognosis of HBP cancers.Thus,not only is RON significant in HBP cancers,but also RON-targeted therapeutics could be developed to treat these cancers,for example,therapeutic monoclonal antibodies and small-molecule inhibitors.Among them,antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.

工程化外泌体在肺癌治疗中的研究进展

非小细胞肺癌最佳的治疗方式为早期手术治疗,而大部分肺癌发现时已为晚期。治疗方式以药物及放射治疗为主。但上述治疗方式出现耐药或疗效不显著是不可避免的,因此,针对肺癌的治疗迫切需要更多的手段。研究证实,工程化外泌体在心血管系统疾病、肿瘤、组织再生与修复等领域具有良好的临床应用潜能。本文总结了国内外工程化外泌体在肺癌治疗中的应用。

G719X/L861Q/S768I突变非小细胞肺癌诊断及靶向治疗进展

肺癌在全球癌症死亡原因中占比最高,对人类健康造成了极大威胁。30%-40%的非小细胞肺癌(non-small cell lung cancer,NSCLC)的发生是由于表皮生长因子受体(epidermal growth factor receptor,EGFR)发生点突变、外显子插入、外显子缺失导致。除常见的19号外显子缺失突变和21号外显子L858R突变外,18号外显子G719X突变、21号外显子L861Q突变、20号外显子S768I突变是最主要的罕见突变。目前,针对主要罕见突变的诊断方法主要是下一代测序技术(next-generation sequencing,NGS)、数字聚合酶链式反应(digital polymerase chain reaction,dPCR)、微滴式数字PCR(droplet digital PCR,ddPCR)等。关于G719X/L861Q/S768I突变NSCLC的靶向治疗,第一代EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)疗效较差,第二代和第三代EGFR-TKIs疗效相当,新型第三代EGFR-TKIs和联合治疗展现出不错的治疗前景。本文对G719X/L861Q/S768I突变NSCLC诊断及靶向治疗进展进行了归纳,以期为后续临床用药及研究提供参考。

原发性肝血管肉瘤1例报告

1病例资料患者男,49岁,因“间断性上腹部疼痛不适10余天”于2020年7月3日入院。患者既往体健,无特殊病史,无化学毒物及放射性物质接触史。入院后,体格检查示右上腹部轻度压痛,余未见明显阳性体征。实验室检查结果示乙型肝炎表面抗原(hepatitis B surface antigen,HBs Ag)、乙型肝炎表面抗体(hepatitis B surface antibody,HBs Ab)、乙型肝炎e抗原(hepatitis B e antigen,HBe Ag)、乙型肝炎核心抗体(hepatitis B core antibody,HBc Ab)均为阳性,HBV DNA为8.14×10^(5)IU/m L,血小板计数为146×10^(9)/L,甲胎蛋白为5.69 ng/m L,其他生化指标未见明显异常。

EGFR外显子20插入突变:研究现状与治疗新策略

作为非小细胞肺癌(non-small cell lung cancer,NSCLC)中重要的致癌驱动基因,表皮生长因子受体外显子20插入突变(epidermal growth factor receptor exon 20 insertion,EGFR ex20ins)具有独特蛋白构象,并且对传统EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)原发耐药。近年来,靶向EGFR ex20ins的药物探索从未停止。莫博赛替尼与埃万妥单抗率先被美国食品药品监督管理局(Food and Drug Administration,FDA)获批用于EGFR ex20ins突变NSCLC患者,随后舒沃替尼等药物取得突破,联合治疗方案的探索也有所收获。多管齐下有望克服EGFR ex20ins耐药。因此,深入了解EGFR ex20ins的分子机制并评估新型药物的有效性与差异性至关重要。本文将对相关最新研究成果进行全面总结,以期为EGFR ex20ins突变患者精准治疗提供有价值的参考。

粒细胞样髓源性抑制细胞在非小细胞肺癌中的研究进展

粒细胞样髓源性抑制细胞(granulocytic myeloid-derived suppressor cells,G-MDSCs)是MDSCs的主要亚群之一,在多数癌症中广泛富集,通过表达精氨酸酶1(arginase-1,Arg-1)及活性氧(reactive oxygen species,ROS)等机制抑制淋巴T细胞杀伤功能,重塑肿瘤免疫微环境,促进肿瘤的发生发展。近年来,越来越多的研究发现G-MDSCs与非小细胞肺癌患者的预后和免疫治疗疗效具有显著相关性,使用特异性靶向G-MDSCs的募集、分化和功能的药物能够有效抑制肿瘤的进展。本文主要就G-MDSCs在非小细胞肺癌中的免疫抑制作用及其相关通路靶向药物的研究进展进行综述。

不可切除胰腺癌的分子靶向药物治疗进展

胰腺癌作为消化系统最常见的恶性肿瘤之一,其发病率及死亡率正逐年上升,大多数胰腺癌患者因分期较晚而失去了手术机会。尽管以吉西他滨、氟尿嘧啶为主的化疗方案在一定程度上延长了患者的生存期,但仍有部分患者因无法耐受化疗而失去治疗机会。随着精准医疗时代的来临,分子靶向药物治疗展现出的优异疗效使其成为对抗肿瘤的重要治疗手段之一,但由于胰腺癌高度的异质性及复杂的免疫微环境,针对胰腺癌的分子靶向治疗并未取得显著效果,因此亟需探寻新的治疗靶点及药物攻克这一难题。本综述基于胰腺癌常见分子靶点及肿瘤免疫相关靶点探究在不可切除胰腺癌中分子靶向药物治疗研究的最新进展,为胰腺癌患者提供新的治疗策略。

EGFR突变可切除的NSCLC围手术期辅助靶向治疗研究进展及问题探讨

肺癌在全球范围内仍是导致癌症死亡的首要原因,非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌的主要病理类型,占80%左右。在所有NSCLC患者中,约30%初诊时为可切除的早中期NSCLC。近期表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)在EGFR突变可切除的NSCLC围手术期辅助靶向治疗中取得重大突破,并被指南推荐应用于临床。本文在总结EGFR突变可切除NSCLC围手术期辅助靶向治疗临床研究进展的基础上,针对临床研究中的关键问题进行探讨。

能谱CT早期评估结直肠癌肝转移化疗联合靶向治疗效果的研究

目的:利用能谱CT早期定量评估结直肠癌肝转移(CRLM)患者一线化疗联合靶向治疗的效果,以提高临床疗效判定能力和有利于优化后续治疗方案。方法:纳入2021年9月至2023年3月在我院就诊的78例结直肠癌肝转移患者,联合靶向治疗2个月后行能谱CT检查,获得病灶门脉期定量参数。患者在接受6个月的治疗后,依照实体瘤疗效评价标准(RECIST1.1),将完全缓解(CR)+部分缓解(PR)+疾病稳定(SD)的患者归入预后较好组,疾病进展(PD)患者归入预后较差组。采用单因素分析方法比较2组间临床基本资料和能谱CT定量参数差异;以多因素回归分析构建模型,绘制受试者工作特征(ROC)曲线,通过曲线下面积(AUC)评估临床能谱CT定量参数模型预测CRLM患者靶向治疗效果的效能。结果:经单因素分析,2组间原发灶N分期、RAS突变和基线癌胚抗原(CEA)水平差异均有统计学意义(均P<0.05);2组间门脉期碘浓度(IC)、标准化碘浓度(NIC)和能谱曲线斜率k_(40-70)差异也均有统计学意义(均P<0.001)。经多因素分析,原发灶N分期、RAS突变和IC是预测CRLM患者早期治疗反应的独立危险因素。结论:能谱CT可早期定量评估CRLM一线化疗方案联合靶向治疗的效果。