Chemotherapeutic advances in pancreatic cancer

Advances in chemotherapy for pancreatic cancer have been limited. In the past decade, the standard therapy for metastatic disease has switched from 5-fluorouracil (5-FU) to gemcitabine. However, several other cytotoxic agents have shown limited but promising efficacy in pancreatic cancer, and many of these appear to be well suited for combination chemotherapy. Although 5-FU and cisplatin have not demonstrated substantial survival benefits when combined with gemcitabine, results of several phase III trials with other agents are still pending. For locally advanced disease, most recent studies have incorporated gemcitabine into combined-modality therapy. Similarly, in surgically resectable disease, current trials are incorporating gemcitabine into adjuvant therapy. Other trials are using neoadjuvant therapy as a possible means to improve upon current surgical results. However, much hope comes from the development of newer “targeted” therapies for this disease. Although matrix metalloproteinase inhibitors and farnesyl transferase inhibitors did not appear to be effective in initial studies, other targeted therapies are beginning to enter clinical trials.     

Recent advances and limitations of surgical treatment for pancreatic cancer

Recent advances in surgical treatment for pancreatic cancer have been remarkable. Pancreatoduodenectomy is a standard surgical procedure for cancer of the pancreatic head, and is now indicated even for elderly patients over 80 years of age. Pancreatoduodenectomy with combined resection of the peripancreatic vessels has improved survival, but extended resection including lymph nodes is considered to have no extra survival benefit. Furthermore, laparoscopic resection procedures including pancreatoduodenectomy, distal pancreatectomy, enucleation and central pancreatectomy can now be performed safely. Neoadjuvant or adjuvant chemotherapy using gemcitabine may further improve the surgical outcome. An understanding of the oncological aspects of pancreatic cancer and the development of surgical techniques and chemotherapy may further contribute to improving the outcome of surgery for pancreatic cancer.     

Recent advances in diagnosis of pancreatic cancer

The clinical course of patients with pancreatic cancer remains dismal. This may be because the pancreas is a retroperitoneal organ, the symptoms are non-specific, occur late, and pancreas cancer has an invasive nature. Screening for asymptomatic or symptomatic patients using serum tumor markers and ultrasonography is not cost-effective. However, the clinical course of small carcinomas less than 1 cm or 1 cm in size is favorable. Thus, the detection of small pancreatic carcinoma is essential to improve the clinical outcome. Possible discovery of pancreatic carcinoma as a diagnostic clue to diabetes mellitus, and intraductal papillary-mucinous neoplasm are introduced based on our clinical experience.     

Novel therapies for pancreatic cancer

To date, pancreatic cancer has proved to be one of the most resistant malignancies, characterized by early local invasion and distant spread. Therefore, resection with curative intent is limited to a very small proportion of patients. Even in this select group, long-term survival remains very poor. Although radiotherapy and chemotherapy may provide some palliative benefits, these interventions have had minimal impact on overall survival. Over the past several years, 2'-difluoro-2'-deoxycytidine (gemcitabine) has demonstrated modest activity in advanced disease, and investigations are proceeding to expand its role in the adjuvant setting, in combination with radiotherapy, and in combination with other agents. In addition, several new cytotoxic agents are being tested for efficacy in pancreatic cancer. Although these drugs may demonstrate clinically meaningful anti-tumor activity, none of them is expected to dramatically alter the natural history of this disease. However, with the identification of the molecular events involved in pancreatic carcinogenesis, invasion, and metastasis, new agents with specific molecular targets are being developed and tested in the clinic. These targets include matrix metalloproteinases, the K-ras oncoprotein, the tumor suppressor p53, HER2, epidermal growth factor receptor, and vascularendothelial growth factor. These molecular approaches provide an exciting opportunity to improve outcomes for patients with pancreatic cancer.     

Recent advances for the treatment of pancreatic and biliary tract cancer after first-line treatment failure

Here, we evaluate clinical trials on chemotherapy for patients with pancreatic or biliary tract cancer after first-line treatment failure. Clinical trials on conventional and innovative medical treatments for progressive pancreatic and biliary cancer were analyzed. Metronomic chemotherapy, which consists of the administration of continuative low-dose of anticancer drugs, was also considered. A significant extension of overall survival was achieved with second-line, regimens in patients with gemcitabine-refractory pancreatic cancer. Moreover, many Phase II studies, including chemotherapy and target molecules and immunotherapy, have reported promising results, in both pancreatic and biliary cancer. However, data in these patients’ setting are very heterogeneous, and only few randomized studies are available.     

2016年胰腺癌研究及诊疗进展

胰腺癌是消化系统恶性程度最高的肿瘤之一,病情进展快,预后极差.近年来,发病率亦明显升高.胰腺癌的治疗模式已由单纯的手术优先,走向包括外科手术、化学治疗和放射治疗等在内的多学科综合治疗,其临床疗效有了明显提高.近年来,随着对胰腺癌发生、发展机制研究的不断深入,研究者对疾病本身有了更加清晰的认识,也为基础临床的转化提供了线索.该研究参考2016年国内外发表的胰腺癌基础和临床研究相关文献,针对胰腺癌发病因素、基础研究热点、外科手术相关进展及化学治疗进展等方面进行综述.     

2015年胰腺癌研究及诊疗前沿进展

随着发病率和死亡率的增加,癌症不仅成为中国疾病致死的重要原因,也同样是困扰世界的一个重大公共卫生问题。尤其令人担忧的是,全世界每年新发胰腺癌病例数呈现逐年上升的趋势。胰腺癌患者的预后较差,其5年生存率仅约6%,其主要原因包括：①在疾病的早期缺乏典型的临床症状,早期诊断困难;②高侵袭转移特性导致难以控制的复发和转移;③缺乏有效的化疗及靶向治疗药物;④容易对现有化疗药物产生耐药。手术根治性切除仍是目前最有效的治疗方式,但是根治术后早期转移复发仍是造成手术预后不良的主要问题。本文将就2015年全球范围内针对胰腺癌发病因素、流行病学调查、基础研究热点、外科手术相关进展、内科治疗和精准医学等方面的研究及诊疗前沿进展进行回顾性分析。     

2017年胰腺癌基础研究及诊疗新进展

胰腺癌是恶性程度极高的消化道肿瘤,疾病进展快,患者预后差,早期病情隐匿;同时手术切除率及化疗有效率低。近年来胰腺癌发病率逐年升高,成为危害人类健康的重大公共卫生问题。随着人们对胰腺癌生物学行为认识的不断加深,基础研究为临床治疗提供了理论依据,并丰富了临床治疗手段。胰腺癌的治疗模式已由单纯的外科治疗过渡到多学科综合诊治的模式。该文参考2017年胰腺癌研究领域发表的最新文献,对胰腺癌流行病学、发病因素、基础热点研究及临床研究新进展进行综述。     

Novel advances in drug delivery to brain cancer

The therapy of brain tumors has been limited by a lack of effective methods of drug delivery to the brain. Systemic administration is often associated with toxic side effects and ultimately fails to achieve therapeutic concentrations within a tumor. An attractive strategy that has gained importance in brain tumor therapy has relied on local and controlled delivery of chemotherapeutic agents by biodegradable polymers. This technique allows direct exposure of tumor cells to a therapeutic agent for a prolonged period of time and has been shown to prolong the survival of patients with malignant brain tumors. The use of polymers for local drug delivery greatly expands the spectrum of drugs available for the treatment of malignant brain tumors. This review discusses the rationale for local drug delivery, describes the development of currently available polymer-based therapeutic agents, and highlights examples of promising non-polymer based drug delivery methods for use in the treatment of malignant brain tumors.     

乳腺癌的生物治疗

手术切除、辅助化疗和放疗被认为是目前乳腺癌的主要治疗方法.随着现代生物工程技术的发展,以分子靶向治疗、基因治疗、免疫治疗等为主要代表的先进生物治疗技术已部分进入乳腺癌的临床研究阶段,显示出较好的耐受性和良好疗效.     

胰腺癌免疫治疗的研究进展

胰腺癌是恶性程度最高的消化系统肿瘤,免疫治疗在胰腺癌领域的研究取得较大进展。目前对免疫检查点的研究主 要集中在细胞毒T淋巴细胞抗原4(cytotoxic T lymphocyte antigen-4,CTLA-4)及程序性细胞死亡分子1 (programmed death-1,PD- 1)/程序性死亡蛋白配体1 (programmed death-ligand 1,PD-L1)等分子的研究。已有大量疫苗应用于胰腺癌：靶向KRas、MUC-1/ CEA、WT1 (Wilms tumor-1) 、热激蛋白、多肽疫苗以及VEGFR2 等,其中取得较好效果的有全肿瘤疫苗(如algenpantucel-L)、端粒 酶多肽疫苗(GV1001)、GVAX瘤苗和WT1疫苗等。T细胞也可以控制胰腺癌的进展,大多数免疫疗法在胰腺癌的临床前期实验 中依靠改进T细胞功能来提高疗效,但未来应用于临床还有待进一步深入研究。     

The advances of Midkine with peripheral invasion in pancreatic cancer

Pancreatic cancer is a deadly malignancy associated with rapid progression and poor prognosis. Perineural invasion (PNI) in pancreatic cancer is one of the most common characteristics of this disease, with incidence of nerve invasion between 53.3% and 90%. PNI is also associated with disease recurrence and pain. Despite research efforts, the detailed mechanisms underlying PNI in pancreatic cancer remains unknown. The main factors of PNI in pancreatic cancer will be introduced in the following: 1. The anatomy of the pancreas nerve: The cancer cells along the blood vessels, lymphatic vessels, peripheral nerve gap and perineurium to Invasion. 2. Adhesion molecules in PNI: Neural cell adhesion molecules. 3. Growth factor: For example, nerve growth factor and tyrosine kinase receptor A; Neurotrophic factor and its receptor, etc. 4. The others: Such as matrix metalloproteinases, integrin. A neurite growth promoting factor and neuritrophic factor known to have a role in the pathophysiology of pancreatic cancer by inducing neuritis growth is midkine. In this review, we discuss the role of midkine and other growth and neurotrophic factors on the pathophysiology of PNI in pancreatic cancer.     

Novel gene therapy approaches to pancreatic cancer

One of the most lethal human malignancies, pancreatic adenocarcinoma has remained a therapeutic challenge. Historically, the only curable treatment modalities available to patients with this disease have included pancreaticoduodenectomy with adjuvant chemoradiation. Few patients, however, have resectable disease at the time of presentation, and even for those who are offered this radical course of treatment, post-surgical survival is dismally short. Recently, however, advances in the understanding of the molecular biology of pancreatic cancer have enabled researchers to investigate novel gene therapy approaches to the treatment of this disease. In this paper, we review the common genetic mutations found in pancreatic adenocarcinomas, discuss strategies for the manipulation of genetic targets, and assess current progress in the field of gene therapy as it relates to pancreatic cancer.     

厄罗替尼靶向治疗肿瘤临床研究进展

表皮生长因子受体（epidermal growth factor receptor,EGFR）是跨膜酪氨酸激酶受体,许多上皮肿瘤均有表达。厄罗替尼是喹唑啉类衍生物,可以选择性、可逆的抑制EGFRTK的活性。本文对厄罗替尼治疗非小细胞肺癌、胰腺癌、头颈部癌进行了综述。     

胰腺癌的治疗进展

外科是胰腺癌惟一可能治愈的手段。放化综合治疗可提高局部晚期患者的中位生存期。抗血管生成是有吸引力的治疗靶标,生物靶向治疗与化疗联合对局部晚期胰腺癌患者有一定的疗效。     

胰腺癌的治疗进展

外科是胰腺癌惟一可能治愈的手段。放化综合治疗可提高局部晚期患者的中位生存期。抗血管生成是有吸引力的治疗靶标,生物靶向治疗与化疗联合对局部晚期胰腺癌患者有一定的疗效。     

Novel protein kinases in pancreatic cell growth and cancer

The network of enzymes that contribute to the signal transduction of extracellular factors in pancreatic cancer is ever increasing. The classical Raf-MEK-ERK signaling cascade plays a crucial role in the regulation of apoptosis, proliferation, and metastasis of pancreatic cancer. Phosphatidylinositide-3-kinase also contributes to growth and prevents apoptosis in pancreatic cancer cells, acting in part via its downstream targets, PKB/AKT and the FRAP/p70^s6k signaling complex. Recently, members of the PKC family of serine threonine kinases have emerged as novel modulators of transformation and cell cycle progression of pancreatic cancers. The novel PKD family of serine threonine kinases has just been detected in pancreatic cancer and awaits its functional characterization in these tumors.