Anti-Cancer Drugs最新文献

FOLFOX combined with cetuximab is a recommended first-line treatment regimen for RAS/BRAF wild-type metastatic colorectal cancer (mCRC). CAPEOX combined with cetuximab differs from the FOLFOX regimen by using oral capecitabine instead of continuous infusion of fluorouracil, offering greater convenience and cost-effectiveness with higher patient acceptance. However, the comparative efficacy of these two regimens remains debatable, necessitating further evidence to explore any differences in their efficacy. This study collected medical records of mCRC patients who were treated with CAPEOX or FOLFOX combined with cetuximab from 1 October 2021 to 16 October 2023 at Harbin Medical University Cancer Hospital and the First Hospital of Shanxi Medical University. Eligible patients were selected based on inclusion criteria and followed up through the hospital's follow-up system and telephone interviews. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were used to assess patients' progression-free survival (PFS) and overall survival (OS). A total of 71 eligible patients were enrolled in this study; 43 patients received CAPEOX combined with cetuximab (Group A, n = 43), and 28 patients received FOLFOX combined with cetuximab (Group B, n = 28). The two groups achieved similar median PFS (mPFS) and median OS (mOS), with mPFS of 18 months and 12 months, respectively (P = 0.23), and mOS of 33 months and 20 months, respectively (P = 0.21), with no statistically significant differences. The results of this study demonstrated that CAPEOX combined with cetuximab is an equally viable option for first-line treatment of RAS/BRAF wild-type mCRC as FOLFOX combined with cetuximab.

We present the case of a young woman diagnosed with chronic myeloid leukemia who began de-novo treatment with nilotinib, which led to increased plasma levels of total bilirubin and QT interval. An evaluation of the genetic profile of uridine diphosphate glucuronosyltransferase was made, as nilotinib inhibits the activity of this enzyme causing hyperbilirubinemia, with higher risk in slow metabolizers, such as those ones with *6/*6 genotype. This type of patient can be identified by genetic profiling, and adjustment in the dose of nilotinib could be made to avoid tyrosine kinase inhibitor switching.

Thyroid cancer is one of the most common endocrine gland malignancies in China. During gene transcription, the bromodomain and extraterminal domain (BET) proteins perform epigenome interpretation tasks. Bromodomain-containing protein 9 (BRD9) is one of the BET family members. Increasing evidence has implicated that BRD9 plays significant roles in multiple malignancies. However, its role in thyroid cancer is still not fully understood. In this research, our results demonstrated that high expression of BRD9 can facilitate the malignant phenotype of thyroid cancer cell lines, while low expression of BRD9 can impede the malignant phenotype of thyroid cancer cell lines. Pharmacologically, I-BRD9 treatment inhibits the proliferation and promotes the rate of apoptosis in thyroid cancer cell lines. Moreover, our results also revealed that BRD9 promoted xenograft tumor growth. In addition, our study showed that the expression of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) pathway-related proteins was decreased in BRD9 knockdown thyroid cancer cells, such as Raf, ERK, p-ERK, c-Fos, and c-Myc, which could be significantly reversed by overexpressing the BRD9 in different thyroid cancer cells. After the specific inhibitor of ERK (SCH772984) was applied to thyroid cancer cells (BCPAP cells) overexpressing the BRD9 gene, the results suggested that SCH772984 reverses the high expression of MAPK/ERK pathway-associated protein in BCPAP cells (over-expression BRD9 cells). In conclusion, this study demonstrated that BRD9 was highly expressed in serum and malignant tumor tissues of thyroid cancer patients and further promoted the development of the malignant phenotype of thyroid cancer by activating the MAPK/ERK signaling pathway.

Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient's sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient's requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths in humans worldwide. Fibroblast growth factor family (FGFs) and the Hippo signaling pathway play an important role in the epithelial-mesenchymal transition (EMT) process of GC. YAP1, a key mediator of the Hippo pathway, plays an important role in tumor genesis. Alternative splicing of human YAP1 mRNA results in two major isoforms: YAP1-1, which contains a single WW domain, and YAP1-2, which contains two WW domains, respectively. There are significant differences in post-transcriptional regulation and function. Basic FGF (bFGF) treatment promoted the EMT process of most GC cell lines, and the proliferation ability was enhanced. This process may be related to the upregulation of YAP1, the proliferation ability of GC was significantly alleviated upon YAP1 knockdown. bFGF treatment can induce EMT of GC through YAP1-2 and enhance their proliferative ability. In this process, bFGF may enhance the nuclear localization of YAP1-2.In the mouse model of intraperitoneal implantation tumorigenesis, it was shown that under the action of bFGF, the expressing YAP1-2 cell lines could form larger tumors than the expressing YAP1-1, but both of them were larger than the YAP1 knockdown. Our results show that YAP1-2 is the main subtype of bFGF-induced EMT and proliferation of GC cells.

Neuron conversion leads to proliferation inhibition of glioma cells and may be an effective strategy to combat glioma and prevent recurrence. In this study, drug repositioning based on Connectivity Map (CMap) was conducted to discover drugs that could induce the differentiation of glioma cells into neuron-like cells, complemented by in vitro experimental validation. Downregulated neuronal genes in glioma were identified by the Human Protein Atlas database and the GeneCards database, and enrichment analysis and Gene Expression Profiling Interactive Analysis (GEPIA) were performed to ensure their reliability before they were uploaded to CMap for drug screening. The potential drug targets were screened through GEPIA and validated by the Chinese Glioma Genome Atlas database. Cell morphology, proliferation, and neuronal marker expression were detected to evaluate the differentiation-inducing effect of the selected drugs. The bioinformatics analysis identified histone deacetylase (HDAC) inhibitors as potential drugs. HDAC1/3/7 showed the relationship with neuronal genes, and HDAC1 showed the highest level of inverse correlation with neuronal gene expression and had the highest hazard ratio. In vitro study showed that both the pan-HDAC inhibitor belinostat, class I and class IIa HDAC inhibitor valproic acid, and selective HDAC1 inhibitor parthenolide induce morphology alteration, proliferation inhibition, expression of neuronal markers including microtubule-associated protein 2, neuronal nuclei antigen, and synaptophysin in U87 cells. This study suggests that the HDAC inhibitors belinostat, valproic acid, and parthenolide can induce glioma cells to differentiate into neuron-like cells, with HDAC1/3/7 being the likely drug targets and HDAC1 potentially playing an important role in this.

Pancreatic cancer ranks fourth among cancer-related deaths with a low 5-year overall survival rate of less than 13%. At present, treatment of pancreatic cancer is still based on chemotherapy, but the efficacy is limited. Thus, a novel therapeutic agent for pancreatic cancer therapy is urgently needed. A library of compounds was screened, and YKL-06-061, a selective inhibitor of salt-inducible kinases (SIKs), was discovered for its ability of inhibiting the proliferation and metastasis of pancreatic cancer cells in vitro and reducing the growth of xenografts in nude mice in vivo . The results from transcriptome analysis showed that YKL-06-061 influenced the mRNA levels of many genes related to c-Myc and SIK1 signals. Based on this, it was found that YKL-06-061 induced cell cycle arrest at the G1 phase and decreased the levels of c-Myc, CDK4, and cyclin D1 protein. At the same time, YKL-06-061 inhibited invasion and metastasis of cancer cells, increased the levels of SIK1 and E-cadherin protein, and lowered vimentin and ZEB-1. Moreover, YKL-06-061 effectively enhanced the antiproliferation of gemcitabine or doxorubicin in pancreatic cancer cells in a synergistic manner. Collectively, these findings implicate YKL-06-061 as a promising therapeutic agent for patients with pancreatic cancer.

This case report highlights sorafenib as maintenance therapy postallogeneic hematopoietic stem cell transplantation (allo-HSCT) in a young patient with acute myeloid leukemia (AML) with FMS-like tirosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation. Given the high relapse risk in FLT3-ITD-positive AML, the tyrosine kinase inhibitor sorafenib was administered. Several studies have shown that sorafenib improves survival in younger AML patients when combined with chemotherapy, though side effects can limit use in older patients. Sorafenib is increasingly significant after allo-HSCT maintenance, offering a promising option for high-risk AML cases. In this case, the patient achieved long-term remission with minimal side effects.

Epidermal growth factor receptor (EGFR) mutations like the common L858R and exon 19 deletions are well studied, but rarer mutations like exon 19 insertions have received less attention. This case report describes a patient with this uncommon EGFR exon 19 insertion mutation in metastatic lung adenocarcinoma. A 51-year-old male nonsmoker with metastatic lung adenocarcinoma and a rare EGFR exon 19 insertion mutation experienced disease progression on initial carboplatin-pemetrexed chemotherapy. However, treatment with the second-generation tyrosine kinase inhibitor afatinib led to a partial response, with significant regression of the primary tumor and bone metastases. This case highlights the favorable clinical response to afatinib treatment in a patient with metastatic nonsmall cell lung cancer harboring a rare EGFR exon 19 insertion mutation.

Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have revolutionized cancer treatment by enhancing the immune system's response to malignancies. However, these therapies are associated with immune-related adverse events (irAEs), including neuromuscular complications such as myasthenia gravis, myositis, and myocarditis. We describe two male patients, aged 67 and 68, with small cell and non-small cell lung cancers, who developed progressive neuromuscular symptoms, including ptosis, diplopia, and generalized weakness, after receiving pembrolizumab. Clinical, biochemical, imaging, and electrophysiological findings confirmed the diagnosis of myositis with myastheniform features, with one case also involving myocarditis. Both patients underwent treatments with intravenous immunoglobulin (IVIg), pyridostigmine, and corticosteroids. The first patient, despite aggressive treatment including plasma exchange and rituximab, succumbed to complications from aspiration pneumonia. The second patient showed partial response to pyridostigmine and IVIg but later died due to metastatic cancer progression. A literature review revealed 52 cases of pembrolizumab-associated myositis with myastheniform symptoms, emphasizing its high morbidity and the need for vigilant monitoring. Pembrolizumab-associated myositis with myastheniform symptoms, especially when accompanied by myocarditis, presents a significant clinical challenge with high mortality. Early recognition and aggressive management of these irAEs are crucial to improving outcomes in cancer patients receiving ICIs.