Anti-cancer Drugs[JOURNAL]
Sun
200 papers
YKL-06-061 exerts antitumor effect through G1/S phase arrest by downregulating c-Myc and inhibition of metastasis via SIK1 upregulation in pancreatic cancer.
Zeng CY, Wang WD, Shang Y … +3 more , Xi SH, Li LP, Chen SZ
Anticancer Drugs · 2025 Feb · PMID 39625737 · Publisher ↗
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....
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.
aYAP1-2 contributes to bFGF-induced proliferation In gastric cancer.
Chen H, Xue DK, Wang YX … +1 more , Jiang TF
Anticancer Drugs · 2025 Feb · PMID 39625344 · Full text
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 t...
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.
Prognostic impact of elevated C-reactive protein and procalcitonin in patients with extensive-stage small cell lung cancer.
Buğday İ, İnanç M, Özkan M … +7 more , Bozkurt O, Coşar R, Firat ST, Mutlu E, Eser M, Dişli AK, Cengiz M
Anticancer Drugs · 2025 Feb · PMID 39601772 · Publisher ↗
Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective w...
Small cell lung cancer (SCLC) constitutes around 15% of lung cancer cases and stands as the primary cause of cancer-related fatalities in men and the second leading cause in women globally. In this study, our objective was to evaluate the levels of C-reactive protein (CRP) and procalcitonin (PCT) in newly diagnosed extensive-stage SCLC patients without evidence of infection. We aimed to demonstrate that elevated CRP and PCT levels may not solely indicate infection but could also be elevated in malignancies. Furthermore, we sought to correlate these marker levels with patient and disease characteristics to elucidate the relationship between these inflammation markers and disease progression. A total of 115 patients who were pathologically and radiologically diagnosed with extensive-stage SCLC between January 2020 and December 2022 and who had received no prior treatment were included in the study. The Kaplan-Meier analysis revealed a median progression-free survival (PFS) of 7.46 months [95% confidence interval (CI), 6.85-8.07] and a median overall survival (OS) of 10.50 months (95% CI, 8.69-12.30) for all patients. In the group with elevated PCT, the median PFS was 6.73 months (95% CI, 3.92-9.54), whereas it was 7.86 months (95% CI, 7.13-8.59) in the group with normal PCT ( P = 0.002). Similarly, the median OS was 9.10 months (95% CI, 5.61-12.58) in the elevated PCT group and 11.66 months (95% CI, 9.59-13.74) in the normal PCT group ( P = 0.006). Patients with elevated procalcitonin (PRC) levels at the time of diagnosis exhibited shorter PFS and OS durations compared to patients with normal PRC levels. Furthermore, elevated CRP has also been demonstrated to correlate with poorer prognosis in extensive-stage SCLC.
Sorafenib as maintenance therapy in FLT3+ acute myeloid leukemia post allogeneic transplantation: a case report.
Martín Roldán A, Alarcón-Payer C, Sánchez Suárez MDM … +1 more , Jiménez Morales A
Anticancer Drugs · 2025 Feb · PMID 39589257 · Publisher ↗
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)-...
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.
Induction of neuronal differentiation in glioma cells by histone deacetylase inhibitors based on Connectivity Map discovery.
Tang ZQ, Xu HB, Cao C … +3 more , Liu YJ, Ye YR, Shen Y
Anticancer Drugs · 2025 Feb · PMID 39589225 · Publisher ↗
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 conduct...
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.
SGPP2 is activated by SP1 and promotes lung adenocarcinoma progression.
Yang X, Wang C
Anticancer Drugs · 2024 Nov · PMID 39514710 · Publisher ↗
The late diagnosis and easy metastasis of lung adenocarcinoma (LADC) remains a challenge. SGPP2 is reported to modulate cell processes in many cancers. However, the roles and molecular mechanisms of SGPP2 in LADC are unc...
The late diagnosis and easy metastasis of lung adenocarcinoma (LADC) remains a challenge. SGPP2 is reported to modulate cell processes in many cancers. However, the roles and molecular mechanisms of SGPP2 in LADC are unclear. Online bioinformatics tools GEPIA, CPTAC, and K-M plotter were used to analyze the expression of SGPP2 and the prognosis in LADC. JASPAR and PROMO were used to predict the transcription factors of SGPP2. Real-time quantitative reverse transcription PCR and western blot were used to detect the levels of SGPP2 in LADC cell lines and tissues. Cell counting kit-8, colony formation, flow cytometry, and transwell assay were used to detect cell proliferation, apoptosis, and invasion. The anti-cancer effect of SGPP2 silence was evaluated in the LADC xenograft model. It was found that SGPP2 was highly expressed and related to the poor prognosis of LADC patients. Elevated SGPP2 expression was detected in LADC cell lines and tissues. The chi-square test indicated that the expression of SGPP2 was positively related to tumor, node, metastasis grades and lymph node metastasis. Knocking down SGPP2 significantly inhibited LADC cell viability, and invasion, but induced apoptosis. The anti-tumor effects of SGPP2 were verified in vivo. The upstream transcription factor of SGPP2 was predicted to be SP1, which was highly expressed in LADC tissues and cell lines. Overexpression of SP1 partly rescued the inhibition of SGPP2-shRNA in cell growth, colony formation, and invasion capabilities, and decreased apoptotic cell number in LADC cells. This study demonstrated that SGPP2, activated by SP1, promotes LADC cell proliferation and invasion, and suppresses apoptosis in LADC.
SMAC mimetic BV6 acts in synergy with mTOR inhibitor to increase cisplatin sensitivity in ovarian cancer.
Chen Q, Zhang H
Anticancer Drugs · 2025 Jan · PMID 39423314 · Publisher ↗
The objective of this study is to observe the antitumor efficacy of the second mitochondria-derived activator of caspases (SMAC) mimetic bivalent smac mimetic (BV6) in combination with target of rapamycin (mTOR) inhibito...
The objective of this study is to observe the antitumor efficacy of the second mitochondria-derived activator of caspases (SMAC) mimetic bivalent smac mimetic (BV6) in combination with target of rapamycin (mTOR) inhibitor on DDP (cisplatin) sensitivity. Ovarian cancer cells were exposed to cisplatin, BV6, DDP + BV6, and DDP + BV6 + mTOR inhibitor Rapamycin. Using proteomics and bioinformatics, protein expression profiles in ovarian cancer were determined. Bagg Albino color nude mice were treated with DDP or BV6 alone or in combination, or BV6 + DDP + Rapamycin. The effects of different treatments on ovarian cancer cells and tumor growth were evaluated in vivo and in vitro . Proteomics and bioinformatics analysis revealed significant changes of protein kinase (AKT)/mTOR pathway. Consistently, western blot data indicated that AKT/mTOR axis was gradually activated in BV6-treated ovarian cancer cells and attenuated the cytotoxic effect of BV6. Functional assays showed that DDP or BV6 treatment alone significantly enhanced the sensitivity and inhibited the migration of ovarian cancer cells, but without any synergistic effects. In addition, combination with BV6 and mTOR inhibitor Rapamycin significantly decreased cell viability and inhibited migration of ovarian cancer cells exposed to DDP. Consistently, the xenograft model showed that co-treatment with Rapamycin with BV6 had significantly suppressed tumor growth and metastasis. Our study demonstrated that SMAC analogue BV6 exhibits a strong anticancer effect on ovarian cancer in vitro and in vivo . Combination with Rapamycin overcomes the activation of mTOR pathway by BV6 and increases the chemosensitivity to DDP. These data suggest a potential application of triple combination with DDP + BV6 + Rapamycin in clinical management of ovarian cancer.
Prophylactic role of pentoxifylline against paclitaxel-induced neuropathy among patients with breast cancer: a randomized-controlled trial.
Kidwani MA, Osama H, Hassan A … +1 more , Abdelrahim MEA
Anticancer Drugs · 2025 Feb · PMID 39423312 · Publisher ↗
Paclitaxel-induced peripheral neuropathy (PN) is a significant clinical concern for which no approved treatment is currently available. The purpose of this trial was to investigate the neuro-prophylactic impact of pentox...
Paclitaxel-induced peripheral neuropathy (PN) is a significant clinical concern for which no approved treatment is currently available. The purpose of this trial was to investigate the neuro-prophylactic impact of pentoxifylline against paclitaxel-induced PN in patients diagnosed with breast cancer (BC). BC patients who were assigned to paclitaxel chemotherapy were randomly allocated to pentoxifylline or a control group for 12 weeks. The main outcomes included the assessment of PN incidence according to the defined Common Terminology Criteria for Adverse Events, quality of life (QoL) using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTx) scale, and neuropathic pain using the scale of self-reported Leeds Assessment for Neuropathic Symptoms and Signs (s-LANSS). The code of the clinical trial registration is NCT06562998. The current study included a total of 72 patients allocated into pentoxifylline arm ( n = 35) and placebo arm ( n = 37). By the 12 th week, the prevalence of PN (grade 2 or 3) was significantly lower in the pentoxifylline arm 10/35 (28.6%) compared to 24/37 (64.9%) of the controls ( P value = 0.016). The total FACT/GOG-NTx score indicated a considerably worse QoL in the control group [98.18 (10.2) vs. 81.43 (14.8) for pentoxifylline and the control group, respectively, P < 0.001] with a mean difference of -16.75 [95% confidence interval (CI): -23.97 to -9.53]. S-LANSS scale showed significantly higher scores after 6 weeks [13.72 (5.86) vs. 17.52 (3.16), P = 0.002] and 12 weeks [17.84 (4.25) vs. 23.80 (1.00), P < 0.001] for pentoxifylline and control group, respectively. In conclusion, the use of pentoxifylline showed a significant reduction in paclitaxel-induced PN, which improved their QoL.
Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.
Fang H, Yang W, Han Q … +8 more , Zhao R, Zheng W, Lu Z, Wu S, Zhu Q, Li J, Guan G, Wen J
Anticancer Drugs · 2025 Jan · PMID 39423045 · Publisher ↗
Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed b...
Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer. However, there is no report on the application in non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) mutation. This case is a patient with EGFR mutant stage IV NSCLC who has progressed after third-line targeted therapy. The fourth line was treated with utidelone combined with pabolizumab. The patient had progressed after targeted therapy with oxitinib, ametinib, and vometinib. Due to the patient's physical reasons, the traditional platinum drugs were not suitable, so the patient was treated with utidelone combined with pabolizumab. The curative effect was evaluated as SD after two cycles and progesterone receptor after four cycles. At present, it is still in the maintenance of reduction of utidelone combined with pabolizumab, and the tumor continues to shrink. Although peripheral neurotoxicity occurred during treatment, it improved after symptomatic treatment. The treatment of EGFR mutant stage IV NSCLC with utidelone combined with pabolizumab has good effect and mild adverse reactions.
KLF4 activates LATS2 to promote cisplatin sensitivity in ovarian cancer through DNA damage.
Ma L, Zhao X, Lu X … +2 more , Shen J, Huang J
Anticancer Drugs · 2025 Jan · PMID 39365847 · Publisher ↗
We aimed to investigate the role of large tumor suppressor kinase 2 (LATS2) in cisplatin (DDP) sensitivity in ovarian cancer. Bioinformatic analysis explored LATS2 expression, pathways, and regulators. Quantitative rever...
We aimed to investigate the role of large tumor suppressor kinase 2 (LATS2) in cisplatin (DDP) sensitivity in ovarian cancer. Bioinformatic analysis explored LATS2 expression, pathways, and regulators. Quantitative reverse transcription-PCR measured LATS2 and KLF4 mRNA levels. Dual-luciferase and chromatin immunoprecipitation assays confirmed their binding relationship. Cell viability, half maximal inhibitory concentration (IC 50 ) values, cell cycle, and DNA damage were assessed using CCK-8, flow cytometry, and comet assays. Western blot analyzed protein expression. The effect of LATS2 on the sensitivity of ovarian cancer to DDP was verified in vivo . LATS2 and KLF4 were downregulated in ovarian cancer, with LATS2 enriched in cell cycle, DNA replication, and mismatch repair pathways. KLF4, an upstream regulator of LATS2, bound to its promoter. Overexpressing LATS2 increased G1-phase cells, reduced cell viability and IC 50 values, and induced DNA damage. Silencing KLF4 alone showed the opposite effect on LATS2 overexpression. Knocking out LATS2 reversed the effects of KLF4 overexpression on cell viability, cell cycle, IC 50 values, and DNA damage in ovarian cancer cells. Inhibiting LATS2 inactivated the Hippo-YAP signaling pathway. In vivo experiments showed that overexpression of LATS2 enhanced the sensitivity of ovarian cancer to DDP. KLF4 activates LATS2 via DNA damage to enhance DDP sensitivity in ovarian cancer, providing a potential target for improving treatment outcomes.
Research on curcumin mediating immunotherapy of colorectal cancer by regulating cancer associated fibroblasts.
Hou C, Hu Y, Zhang T
Anticancer Drugs · 2025 Jan · PMID 39264802 · Publisher ↗
The objective was to investigate curcumin's (Cur) function and associated molecular mechanisms in regulating tumor immunity in colon cancer. Primary cancer-associated fibroblasts (CAFs) from mouse CT26 colon cancer tumor...
The objective was to investigate curcumin's (Cur) function and associated molecular mechanisms in regulating tumor immunity in colon cancer. Primary cancer-associated fibroblasts (CAFs) from mouse CT26 colon cancer tumors were isolated. Validation of primary CAFs using immunofluorescence assay was done. Cell Counting Kit-8 experiments, real-time quantitative PCR (qPCR), and enzyme linked immunosorbent assay experiments were conducted to investigate how curcumin affected the growth and cytokine secretion functions of CAFs. The effect of curcumin on regulating PD-L1 expression on CT26 cells through CAFs in vitro was explored through coculture of CAFs and tumor cells, qPCR, and western blot experiments. A mouse colon cancer cell model was established in Balb/c nude mice to explore the effect of curcumin on colon tumor cells. Changes in the tumor microenvironment were detected by flow cytometry to explore the synergistic effect of curcumin combined with anti-PD-1 monoclonal antibody in the treatment of mouse colon cancer. In vitro, curcumin prevented the growth and TGF-β secretion of CT26 cells. At the same time, curcumin inhibited the secretion of TGF-β by CAFs, thereby downregulating the PD-L1 expression of CT26 cells. In vivo, curcumin combined with anti-PD-1 antibodies can further enhance the inhibitory effect of PD-1 antibodies on tumors and increase the number of tumor-suppressing immune cells in the tumor microenvironment, such as M1 macrophages and CD8 T cells, thus inhibiting tumors. Immune M2 macrophages, regulatory T cells, and other cells were reduced. In conclusion, curcumin reduces the expression of PD-L1 in colon cancer cells and improves the tumor immune microenvironment by inhibiting the proliferation of CAFs and the secretion of TGF-β. Curcumin and anti-PD-1 treatment have synergistic inhibitory effects on colon cancer.
EP-0108A is a moderation selectively BRD4 BD2 inhibitor with potential AML tumor suppression.
Li L, Zhu H, Liu S
Anticancer Drugs · 2025 Jan · PMID 39259687 · Publisher ↗
Acute myeloid leukemia is the most common type of acute leukemia in adults. The epigenetic molecule BRD4 is a member of the bromodomain and extra-terminal family and plays an important role in the occurrence and developm...
Acute myeloid leukemia is the most common type of acute leukemia in adults. The epigenetic molecule BRD4 is a member of the bromodomain and extra-terminal family and plays an important role in the occurrence and development of tumors. BRD4 is essential for oncogene expression, including c-Myc. So, BRD4 inhibition is considered as an effective strategy for the treatment of hematological and solid malignancies. In recent years, several small molecule inhibitors targeting BRD4 have been developed. However, these inhibitors had excessive hematological toxicity due to the lack of specific binding to BD1 and BD2 domains of BRD4, while other inhibitors with high selectivity lose their antitumor efficacy. To balance the relationship between efficacy and safety, we developed EP-0108A, a BRD4 inhibitor with moderate selectivity for the BD2 domain over BD1 domain of BRD4. Our results show that EP-0108A has antitumor effects in MV4-11 and Kasumi-1 cell line-derived xenograft mouse models without significant effects on heart or breathing safe in rats and Beagle dogs. In repeated dose toxicity studies, EP-0108A showed reversible hematological and gastrointestinal toxicity in both rats and dogs. Our findings indicate that EP-0108A has the potential to be a new therapeutic agent for the treatment of cancer.
Synergistic combination effect of the PCA-1/ALKBH3 inhibitor HUHS015 on prostate cancer drugs in vitro and in vivo.
Mabuchi M, Tsujikawa K, Tanaka A
Anticancer Drugs · 2025 Jan · PMID 39259581 · Publisher ↗
Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated wit...
Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated with other cancers. The ALKBH3 inhibitor HUHS015 was found to be effective against prostate cancer both in vitro and in vivo . Herein, we investigated the effect of HUHS015 in combination with drugs for prostate cancer approved in Japan (including bicalutamide, cisplatin, mitoxantrone, prednisolone, ifosfamide, tegafur/uracil, docetaxel, dacarbazine, and estramustine) by treating DU145 cells with around IC 50 value concentrations of these drugs for 3 days. Additionally, the cells were observed for additional 9 days after drug removal. Combination treatment with dacarbazine, estramustine, tegafur/uracil, and HUHS015 showed a slight additive effect after 3 days. After drug washout of them and mitoxantrone, the combined effects and levels were enhanced and sustained, although the effects of each treatment alone declined. HUHS015 combined with cisplatin or docetaxel elicited synergistic and sustained effects. In vivo , combining HUHS015 and docetaxel, the first chemotherapeutic agent for castration-resistant prostate cancer, showed notable effects in the DU145 xenograft model. In conclusion, HUHS015 exhibited a synergistic effect with docetaxel and drugs acting on DNA in vitro , even after drug removal. Since cancer chemotherapy is typically administered during rest periods due to its high toxicity, combining it with an ALKBH3 inhibitor could be a promising strategy for enhancing cancer treatment, as it can elicit an additive effect during treatment, allowing dosage reduction, and synergistically sustain the effect after drug washout during rest periods.
Holding the therapy in CLLp53: mechanisms to achieve durable responses.
Cantera R, Fernández-Barge T, Salmanton-García J … +1 more , Yáñez L
Anticancer Drugs · 2025 Jan · PMID 39133031 · Publisher ↗
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...
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. Herein, we discuss the effects of B-cell receptor and BCL-2 inhibition, as well as the role of the immune system, in two elderly CLLp53 patients with prolonged responses to different therapies.
Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer.
Li C, Mao Y, Liu Y … +5 more , Hu J, Su C, Tan H, Hou X, Ou M
Anticancer Drugs · 2025 Jan · PMID 39132895 · Publisher ↗
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...
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. We then explored the immune infiltration landscape in two groups using the nine algorithms and found more overall immune infiltration in the high-MPCDI group. TIDE scores suggested that the increased immune evasion potential and immune checkpoint inhibition therapy may be less effective in the high-MPCDI group. Immunophenoscores indicated that anti-PD1, anti-cytotoxic T-lymphocyte associated antigen 4 (anti-CTLA4), and anti-PD1-CTLA4 combination therapies are less effective in the high-MPCDI group. In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients.
Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.
Cosso F, Lavacchi D, Messerini L … +9 more , Briganti V, Castiglione F, Brugia M, Berti V, Fancelli S, Cianchi F, Vannini A, Pillozzi S, Antonuzzo L
Anticancer Drugs · 2025 Jan · PMID 39119711 · Full text
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 pe...
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. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.
HER2 exon 20 mutant non-small cell lung cancer with complete remission of intracranial metastases with trastuzumab deruxtecan: a case report.
Güren AK, Kocaaslan E, Ağyol Y … +9 more , Majidova N, Sever N, Erel P, Çelebi A, Arikan R, Işik S, Sari M, Bayoğlu İV, Köstek O
Anticancer Drugs · 2024 Sep · PMID 39115060 · Publisher ↗
Trastuzumab deruxtecan (T-DXd) is a novel anti-HER2 antibody-drug conjugate formed by the combination of trastuzumab and deruxtecan. It is used in human epidermal growth factor 2 receptor (HER2) mutant breast, stomach an...
Trastuzumab deruxtecan (T-DXd) is a novel anti-HER2 antibody-drug conjugate formed by the combination of trastuzumab and deruxtecan. It is used in human epidermal growth factor 2 receptor (HER2) mutant breast, stomach and colorectal cancers as well as non-small cell lung cancer (NSCLC). The 58-year-old denovo metastatic NSCLC patient we will discuss here progressed with newly developing brain metastasis under first-line carboplatin/paclitaxel treatment. After next generation sequencing revealed a mutation in the ERBB2 gene located in exon 20, we administered T-DXd to our patient. While a significant improvement was observed in the clinical condition of the patient after one course of treatment, brain metastases were found to be in complete response in control screening after four courses of treatment. Systemic screening with PET/computed tomography showed nearly complete regression of the primary lesion, metastatic lymphadenopathies, and surrenal metastases. T-DXd may be successfully used in HER2 mutant metastatic NSCLC patients. In addition, it can also be successfully used in patients with central nervous system metastases with or without cranial radiotherapy.
MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient.
Pluchino M, Testi I, Minari R … +10 more , Dodi A, Airò G, Mazzaschi G, Verzè M, Adorni A, Gnetti L, Azzoni C, Lagrasta CAM, Pecci F, Tiseo M
Anticancer Drugs · 2024 Sep · PMID 39115059 · Publisher ↗
The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and M...
The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab. After 18 months since the start of immunotherapy, computed tomography scan showed disease progression and a second-line therapy with dabrafenib and trametinib was initiated. Seven months later, due to a suspect disease progression, a left supraclavicular lymphadenectomy was performed and next-generation sequencing analysis revealed the appearance of MET exon 14 skipping mutation, while fluorescence in situ hybridization analysis showed MET amplification. The patient is still on BRAF and MEK inhibitor treatment. Our case highlights the relevance of performing tumor tissue rebiopsy at the time of progression during treatment with BRAF/MEK inhibition with the aim of identifying putative mechanisms of resistance.
Integrated single-cell and bulk RNA sequencing analyses identify an immunotherapy nonresponse-related fibroblast signature in gastric cancer.
Peng Q, Zhang P, Liu G … +1 more , Lu L
Anticancer Drugs · 2024 Nov · PMID 39110142 · Publisher ↗
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 treat...
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. The R package 'Seurat' was used for scRNA-seq data processing. Cellular infiltration, receptor-ligand interactions, and evolutionary trajectory analysis were further explored. Differentially expressed genes affecting overall survival were obtained using the limma package. Weighted Gene Correlation Network Analysis was used to identify key modules of immunotherapy nonresponder. Prognostic model was constructed by univariate Cox and least absolute contraction and selection operator analysis using the intersection of activated fibroblast genes (AFGs) with key module genes. The differences in clinicopathological features, immune microenvironment, immunotherapy prediction, and sensitivity to small molecule agents between the high- and low-risk groups were further investigated. Based on scRNA-seq, we finally identified 20 AFGs associations with the prognosis of GC patients. AFGs' high expression levels were correlated with both poor prognosis and tumor progression. Three genes ( FRZB , SPARC , and FKBP10 ) were identified as immunotherapy nonresponse-related fibroblast genes and used to construct the prognostic signature. This signature is an independent significant risk factor affecting the clinical outcomes of GC patients. Remarkably, there were more CD4 memory T cells, resting mast cells, and M2 macrophages infiltrating in the high-risk group, which was characterized by higher tumor immune exclusion. Moreover, patients with higher risk scores were more prone to not respond to immunotherapy but were more sensitive to various small molecule agents, such as memantine. In conclusion, this study constructed a fibroblast-associated ICI nonresponse gene signature, which could predict the response to immunotherapy. This study potentially revealed a novel way to overcome immune resistance in GC.
Biomarker-stratified first-line treatment of right-sided metastatic colon cancer with interdisciplinary collaboration in the IVOPAK II trial.
Vitali F, Merkel S, Schubart C … +7 more , Schmid A, Eckstein M, Stöhr R, Kersting S, Hartmann A, Grützmann R, Wein A
Anticancer Drugs · 2024 Oct · PMID 39109395 · Publisher ↗
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 imp...
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. RAS mutation: n = 20 (80%): received systemic first-line treatment: FOLFIRI plus bevacizumab. All-RAS-wildtype: n = 5 (20%): received systemic first-line treatment: FOLFIRI plus cetuximab. Last date evaluation: 31 January 2024. Median age: 59.6 years (range 42-71), men/women: 14/11. Eastern Cooperative Oncology Group (ECOG) index: 0/1/2 : 11/10/4. Evaluable for response: n = 25. Complete response: n = 0, partial response: n = 14 (56%), stable disease: n = 8 (32%), progressive disease: n = 3 (12%), early tumor shrinkage: n = 13 (52%), estimates progression-free survival: 13 months (95% CI 8-17 months), estimated OS: 48 months (95% CI 25-71 months), median follow-up: 26 months (1-61 months), no evidence of disease: n = 4 (16%). A chemotherapy doublette regimen with FOLFIRI plus a biological as first-line treatment shows promising efficacy and secondary metastatic resection after interdisciplinary discussion was associated with a survival benefit in right-sided metastatic colon carcinoma.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe