Anti-cancer Drugs

Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro, facilitating the identification of kinase vulnerabilities to target therapeutically...

Chronic lymphocytic leukemia (CLL) is a common leukemia, mainly affecting the elderly. Originating in the bone marrow, CLL involves the accumulation of B lymphocytes and progresses slowly, though 50-60% of patients will require therapy. At diagnosis, the presence of p53 protein aberrations, such as 17p deletion and TP53 mutation, arises in approximately one out of 10 patients. Even in the era of targeted therapies, these aberrations remain the most important prognostic factors. Current guidelines favor continuous BTK inhibitor therapy in patients with CLLp53, though adverse events and drug resistance may lead to discontinuation...

Tumorigenesis and treatment are closely associated with various programmed cell death (PCD) patterns. However, the coregulatory role of multiple PCD patterns in colorectal cancer (CRC) remains unknown. In this study, we developed a multiple PCD index (MPCDI) based on 19 PCD patterns using two machine learning algorithms for risk stratification, prognostic prediction, construction of nomograms, immune cell infiltration analysis, and chemotherapeutic drug sensitivity analysis. As a result, in the TCGA-COAD, GSE17536, and GSE29621 cohorts, the MPCDI can effectively distinguished survival outcomes in CRC patients and served as an independent factor for CRC patients...

Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer...

Patients with right-sided metastatic colon carcinoma have a significantly worse prognosis than those with left-sided colorectal cancer (CRC), regardless of treatment. The aim of the prospective IVOPAK II study was to implement an interdisciplinary guideline-conform personalized CRC palliative therapy of metastatic colorectal carcinoma and to improve the overall survival (OS) by multidisciplinary approach via secondary metastatic resection. We present the efficacy data of first-line treatment and the benefit of interdisciplinary collaboration of right-sided metastatic colon carcinoma patients: n = 25...

Liposarcoma is one of the most common soft tissue malignancies. We previously discovered upregulation of minichromosome maintenance 2 (MCM2) expression in liposarcoma tissues. Hereon, we attempt to clarify the biological influence and mechanisms of MCM2 in liposarcoma. The mRNA level of MCM2 expression was detected through the use of quantitative real-time PCR. Immunohistochemistry staining and western blot were employed to detect protein expression of MCM2. The protein expression of fibroblast-activation protein and α-smooth muscle actin was examined by immunofluorescence...

Factors that determine nonresponse to immune checkpoint inhibitor (ICI) remain unclear. The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for cancer treatment. There is, however, a lack of CAF-related signature in predicting response to immunotherapy in gastric cancer (GC). Single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data of GC immunotherapy were downloaded from the Gene Expression Omnibus database. Bulk RNA-seq data were obtained from The Cancer Genome Atlas...

Uveal melanoma is the most common intraocular malignancy in adults. Despite advances in local treatments, approximately 50% of all cases eventually die from metastatic disease. In cases with metastasis, 2- and 5-year survival rates are approximately 10% and <1%, respectively. Advances in molecular biology have led to the identification of a number of promising drugs including immune checkpoint inhibitors (ICIs). Ipilimumab and nivolumab are ICIs targeting the cytotoxic T-lymphocyte-associated antigen-4 and the programmed-cell death protein-1, respectively...

Cisplatin is crucial in management of advanced stomach adenocarcinoma, whereas development of chemotherapy resistance hinders overall efficacy of cisplatin. This work aims to explore role of CDC25B in cisplatin sensitivity in stomach adenocarcinoma and offer a possible mechanism for explaining its function. By using bioinformatics approaches, CDC25B and TEAD4 expression levels in stomach adenocarcinoma tissues and enriched pathways of CDC25B were analyzed. qRT-PCR of CDC25B and TEAD4 expression in stomach adenocarcinoma cells, CCK-8 detection of cell viability and IC50 values, and colony formation assay on cell proliferation were performed...

The tumor suppressor gene BRCA1 associated protein-1 (BAP1) is frequently mutated in renal cell carcinoma (RCC). BAP1 loss-of-function mutations are associated with poor survival outcomes. However, personalized therapy for BAP1-mutated RCC is currently not available. Previously, we found that BAP1 loss renders RCC cells more sensitive to bromodomain and extra-terminal (BET) inhibitors, as demonstrated in both cell culture and xenografted nude mice models. Here, we demonstrate that BAP1 loss in murine RCC cells enhances sensitivity to BET inhibitors in ectopic and orthotopic allograft models...

Rituximab is an anti-CD20 chimeric murine/human mAb mainly used to treat certain types of lymphoproliferative malignancies and autoimmune diseases. Although it has been used in the treatment of vasculitis in recent years, it rarely triggers severe vascular skin reactions such as leukocytoclastic vasculitis (LCV). Physicians should be aware of this rare adverse event that requires discontinuation of rituximab, which can occur days or even weeks after rituximab treatment. Here, we report a case of LCV observed in a patient with low-grade orbital B-cell lymphoma treated with weekly rituximab and local radiotherapy...

Retinoblastoma (RB) is the most common primary intraocular malignant tumor of childhood. Persistent or recurrent vitreous seeding is the most common reason for therapeutic failure in advanced RB. Intravitreal chemotherapy has emerged as an effective therapy for vitreous seeding in RB, with a generally acceptable safety profile. However, intravitreal chemotherapeutics, especially melphalan, can cause toxicity that may progress to total retinal atrophy. In this report, we present two cases with retinal melphalan toxicity that had varied clinical findings...

Cervical cancer is among the most common gynecological malignancies. G protein-coupled estrogen receptor (GPER) is involved in the development of various tumors; however, its role in cervical cancer remains unclear. We investigated whether G15, an inhibitor of GPER, can regulate its expression and affect cervical cancer progression. We examined the biological behaviors of G15-treated SiHa and HeLa cells using Cell Counting Kit-8, monoclonal proliferation, plate scratching, and Transwell invasion experiments...

Chemotherapies are standard care for most cancer types. Pyrimidine analogs including 5-fluorouracil, cytosine arabinoside, 5-azacytidine, and gemcitabine are effective drugs that are utilized as part of a number of anticancer regimens. However, their lack of cell-specificity results in severe side effects. Therefore, there is a capacity to improve the efficacy of such therapies, while decreasing unwanted side effects. Here, we report that while 5-fluorocytosine is not chemotherapeutic in itself, incorporated into a ribonucleoside and more importantly into an RNA oligonucleotide, it induces cytotoxic effects on cancer cells in vitro...

Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot...

Nephrotoxicity is one of the most important complications in cancer patients under treatment with cisplatin-containing regimens. Curcumin, as the most important active component of Curcuma longa, is an antioxidant and anti-inflammatory compound. In this clinical trial, we assessed the preventive effect of nano-curcumin oral formulation against cisplatin-induced nephrotoxicity in cancer patients. In this triple-blind clinical trial 30 cancer patients on cisplatin were randomly included in the treatment group, receiving nano-curcumin 40 mg capsules (n = 15) or the placebo group (n = 15) twice a day during four chemotherapy courses...

The current treatment for osteosarcoma (OS) is based on surgery combined with systemic chemotherapy, however, gene therapy has been hypothesized to improve patient survival rates. The density-enhanced protein domain 1 protein (DEPDC1) functions as a crucial determinant in the advancement of OS, which is highly expressed in OS cells. The current study was designed to delve into the effect and mechanism of DEPDC1 and phosphotyrosine-picked threonine tyrosine kinase (TTK) in OS. The expression of DEPDC1 and TTK in OS cells was detected by western blotting...

Metastatic spread to the central nervous system (CNS) is frequent in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) and has an important impact on patient prognosis and quality of life. Leptomeningeal involvement may occur in up to 10% of cases of ALK-positive NSCLC. Lorlatinib is a third-generation ALK inhibitor that has excellent CNS penetrability and demonstrated its efficacy both in pretreated and treatment-naive patients. Herein, we present the case of a 34-year-old patient diagnosed with stage IV ALK-rearranged NSCLC who received two lines of ALK inhibitors (crizotinib followed by alectinib) and several courses of brain stereotactic ablative radiotherapy until leptomeningeal involvement was detected...

Chemoresistance largely hampers the clinical use of chemodrugs for cancer patients, combination or sequential drug treatment regimens have been designed to minimize chemotoxicity and resensitize chemoresistance. In this work, the cytotoxic effect of cisplatin was found to be enhanced by palbociclib pretreatment in HeLa cells. With the integration of liquid chromatography-mass spectrometry-based proteomic and N-glycoproteomic workflow, we found that palbociclib alone mainly enhanced the N-glycosylation alterations in HeLa cells, while cisplatin majorly increased the different expression proteins related to apoptosis pathways...

We present a case of a patient diagnosed with FLT3 mut+ acute myeloid leukemia with FLT3 and NMP1 mutations who did not respond to standard induction and consolidation treatment with chemotherapy. Due to the FLT3mut+ gene mutation and intermediate cytogenetic risk, treatment with gilteritinib is requested. After treatment she experienced a neutrophilic dermatosis and granuloma annulare that was resolved with gilteritinib dose reduction and specific treatment in coordination with the dermatology department.