Targeted therapy has fundamentally altered the diagnosis and treatment of clinical cancers. By focusing on chromosomal abnormalities and various indications of cancer, these medications have paved the way for the precise treatment of malignant tumors. In addition to markedly reversing the status quo of reliance on radiotherapy, chemotherapy, and surgery, these drugs have radically transformed the clinical treatment of advanced malignant tumors and became the leading candidates in the fight against cancer. Significant advancements in new targeted medications, including small molecules (e.g., KRASG12C inhibitors), bispecific antibodies, antibody drug conjugates, and cellular immunotherapy, are due to the advent of new technology and treatments. Notably, numerous difficulties have been encountered, although each medicine class has its own unique benefits and drawbacks. To serve as a key summary for the development of new treatment options for precision cancer medicine recently, this review aimed to summarize the most recent anti-tumor revolutionary medications with significant prospective therapeutic advantages.
Pancreatic cancer is a highly aggressive disease, which is often diagnosed late. Consequently, metastasis is common among newly diagnosed patients, leading to a poor prognosis and high mortality rates. The tumor microenvironment of pancreatic cancer, which comprises pancreatic cancer cells, stromal cells, and immune cells, as well as a multitude of extracellular components, plays a pivotal role in cancer progression and metastasis. Conventional immunotherapies focused on targeting the adaptive immune response have achieved suboptimal outcomes in patients with pancreatic cancer. Thus, the focus has shifted toward targeting innate immune cells, which can infiltrate the pancreatic tumor and contribute to the development and maintenance of the immunosuppressive microenvironment to promote tumor growth and metastasis. This review focuses on the roles of innate immune cells and their interactions in the shaping of an immunosuppressive tumor microenvironment to promote the metastasis of pancreatic cancer. In addition, we review strategies that target innate immune cells to remodel the immunosuppressive tumor microenvironment and improve the prognosis of pancreatic cancer.
We have developed a tridirectional regimen combining intraperitoneal, intravenous, and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression. This multicenter Phase III umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy.
BRCA1/TOPO1 mRNA expression was examined in all enrolled patients. The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm. Patients in the control arm received systemic intravenous/oral chemotherapy, whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy. The primary endpoint was progression-free survival and the secondary endpoints were response rate, overall survival, and safety.
Overall, 233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The objective response rate was 33.9% in the control arm and 49.1% in the individualized arm (P = 0.039). In the control and individualized arms, median progression-free survival was 5.9 months and 8.0 months, respectively (hazard ratio 0.521, 95% confidence interval 0.362–0.750, P = 0.0005) and median overall survival was 13.5 months and 16.4 months, respectively (hazard ratio 0.684, 95% confidence interval 0.474–0.988, P = 0.0430). Both regimens were tolerable.
The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer.
Chinese Clinical Trial Registry (chictr.org.cn) Identifier: ChiCTR-IPR-15006201.
Postoperative anastomotic leak is a threatening complication after esophagectomy. This study aims to evaluate the efficacy of endoscopic naso-leakage negative pressure drainage for anastomotic leak by longitudinal analyses, so as to focus on the intra-individual changes associated with the drainage in the disease course and to minimize the between-subject variations.
We conducted a retrospective longitudinal study. We hypothesize that maximum temperature (Tmax), maximum heart rate (HRmax), White blood cell count (WBC), and C reactive protein (CRP) had a two-piece linear spline growth curve with a notch at the time of drainage. Linear mixed-effects regressions were used to test the hypothesis of whether endoscopic naso-leakage negative pressure drainage changed the pattern of development of these clinical parameters with time.
Thirty patients were included, among which 83.3% were male, with a median age of 77 years. The median postoperative time to drainage was 16.5 days (range 6-66). Observations for Tmax, HRmax, WBC, CRP and PCT were 1366, 1372, 394, 296 and 290, respectively. After adjusting for age, sex, and body mass index, Tmax, HRmax, WBC and CRP showed similar pattern. There was no significant change over time before naso-leakage negative pressure drainage, while the four parameters all decreased significantly over time after naso-leakage negative pressure drainage.
The slope over time of Tmax, HRmax, WBC and CRP changed significantly after naso-leakage negative pressure drainage. Naso-leakage negative pressure drainage brought gradual decrease of these inflammatory parameters and could serve as a promising management for postoperative anastomotic leak after esophagectomy.
Neuroendocrine carcinomas (NECs) of the esophagus are extremely rare and poorly understood. This study aimed to delineate the clinicopathological and immunohistochemical features of esophageal NECs using a retrospective survey.
Patients with histologically proven esophageal neuroendocrine carcinomas (NECs) were recruited from Zhongshan Hospital, Fudan University, China, between 2006 and 2016. Clinical, endoscopic, pathological, and immunohistochemical data were collected retrospectively.
Of 43 patients with NEC, older male patients were predominant. In total, 93.0% of the tumor masses were located in the middle or lower esophagus. Twenty-nine (67.4%) and 22 (51.2%) cases showed ulceration and esophageal stenosis, respectively. The average index of Ki-67 staining was 67.1% ± 21.4% with positive immunostaining for CD56 (88.4%), chromogranin A (51.2%), and synaptophysin (72.1%). Small cell carcinomas accounted for 95.3% of cases, and 16.3% of patients had mixed components with adenocarcinoma or squamous cell carcinoma.
Esophageal NECs are rare and mainly affect men in their sixties or seventies. They show a similar endoscopic appearance to squamous cell carcinoma or adenocarcinoma and present with a proliferative mass with stenosis or ulcers. Therefore, esophageal NECs are difficult to diagnose by endoscopy. Esophageal NECs can be mixed with other subtypes of neoplasms, such as adenocarcinoma and squamous cell carcinoma. In addition to chromogranin A, synaptophysin, and CD56, NSE, S100, and CKpan might be candidate biomarkers to diagnose esophageal NECs. Overall, we provide new insights into the biology of esophageal NECs.