SLFN11, a DNA/RNA helicase implicated in replication stress response, has recently emerged as a pivotal determinant of chemotherapy sensitivity across multiple cancer types. The expression level of SLFN11 in various cancers is significantly positively correlated with the sensitivity of cancer cell DNA damage agents. SLFN11 exerts its chemosensitizing effects by RPA-coated single-stranded DNA (ssDNA) at stressed replication forks at stalled replication forks, thereby potentiating the cytotoxicity of platinum agents, topoisomerase inhibitors, and PARP inhibitors. Its roles in inhibiting ATR translation, mediating p53-independent apoptosis, sensitizing towards IFN-γ and enhancing chromatin accessibility also remain investigational. The down-regulation of SLFN11 expression is associated with epigenetic silencing including promoter methylation, histone deacetylation, and the histone methylation. In this paper, we reviewed the recent progress of SLFN11 as predictive biomarker and therapeutic target in multiple cancers including medulloblastoma, prostate cancer, breast cancer, ovarian cancer, lung cancer, head and neck cancer, esophageal carcinoma, gastric carcinoma and colorectal cancer. We also summarized 10 active clinical trials conducting molecular analyses to assess SLFN11's role. By bridging mechanistic understanding with translational opportunities, this review provides a roadmap for leveraging SLFN11 to overcome chemoresistance and advance precision oncology.

Dendritic cells (DCs) derived extracellular vesicles represent a promising vehicle for the activation of adaptive immunity, demonstrating significant potential in the development of cancer nanovaccines. The aim of this study was to evaluate the antitumor efficacy of a functional DCs-derived extracellular vesicles in castration-resistant prostate cancer.

Colorectal cancer (CRC) is among the most prevalent malignant tumors in the digestive system and is the third leading cause of cancer-related mortality. In recent years, immunotherapy has markedly enhanced the objective response and survival rates for CRC patients. However, the therapeutic efficacy of immunotherapy remains insufficient for the majority of proficient mismatch repair (pMMR) CRC patients, with 20% to 30% of deficient mismatch repair (dMMR) patients demonstrating poor responses or developing drug resistance. Increasing evidence underscores the critical role of intestinal microorganisms in modulating the effectiveness of immunotherapy, particularly in regulating the tumor microenvironment (TME).

There is a continuous increase in the incidence of thyroid cancer. A deeper understanding of the molecular mechanisms of thyroid cancer could significantly improve thyroid cancer management. Newly discovered type of programmed cell death, ferroptosis, has been demonstrated to play a crucial role in many cancers. Mounting evidence shows that there is a close association between ferroptosis and thyroid cancer, which offer a promising therapeutic strategy for thyroid cancer. Ferroptosis is expected to emerge as a novel therapeutic target. Regrettably, the exact role of ferroptosis in thyroid cancer is not yet completely understood. Further, there is currently no summary of ferroptosis in thyroid cancer progression and treatment. Hence, in this review, we aim to revisit the pathological process of thyroid cancer and reveal the role of ferroptosis in thyroid cancer. In addition, we provide evidence that ferroptosis inducers could suppress the growth of thyroid cancer cells. Lastly, we discuss the potential application of ferroptosis inducers in thyroid cancer treatment, as well as possible impediments and corresponding strategies. The relationship between ferroptosis and thyroid cancer will be better understood through this review, which may offer a novel insight into thyroid cancer therapy.

Cadonilimab provides substantial clinical benefits in recurrent or metastatic cervical cancer (R/M CC) in several clinical trials and meeting abstracts. However, the efficacy of cadonilimab in patients with prior failure of anti- programmed death receptor-1 (PD-1) inhibitors, as well as a direct comparison of its efficacy and safety with anti-PD-1 inhibitors, has not been reported in real-world settings.

This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and immunotherapy and explore its potential as a conversion treatment for unresectable hepatocellular carcinoma (uHCC).

Immunotherapy-induced pseudomembranous colitis (PMC) is an uncommon but increasingly recognized adverse effect of immune checkpoint inhibitors, particularly in patients with advanced malignancies. We present a case of a 68-year-old male with gastric adenocarcinoma undergoing treatment with immunotherapy and chemotherapy, who developed symptoms of PMC. Workup for Clostridium difficile and other common etiologies was negative. Colonoscopy revealed severe mucosal congestion and yellowish-green exudates, consistent with PMC. Based on the biopsy results and clinical presentation, after excluding common etiologies, immunotherapy-induced PMC was suspected. The patient responded to steroid therapy, with gradual improvement and a tapering regimen upon discharge. This case underscores the diagnostic challenges in identifying the etiology of PMC, particularly when it presents with diffuse involvement of the colon, which is an uncommon presentation for immunotherapy-related colitis. The overlap in clinical, endoscopic, and histopathological findings with other forms of colitis, such as Clostridium difficile infection (CDI) and inflammatory bowel disease, highlights the need for heightened awareness among clinicians. This case highlights the diagnostic challenges in recognizing immunotherapy-induced PMC, particularly with atypical, diffuse colonic involvement. The overlapping features with other colitis make timely diagnosis difficult. Further research is needed to refine diagnostic criteria and management strategies for immunotherapy induced colitis (IMC).

We developed a novel FTY720 prodrug (pro-FTY) that specifically inhibits sphingosine-1-phosphate signaling in cancer cells using a novel drug delivery system that reacts with acrolein. Our objective was to evaluate the efficacy and safety of pro-FTY in preclinical experiments. Ten breast cancer cell lines, two multidrug-resistant cell lines, and one normal mammary cell line were used to compare the IC50 values of pro-FTY with those of other drugs. Patient-derived organoids (PDO) were established and utilized for IC50 value comparisons. Drug efficacy was tested in mice bearing either syngeneic 4T1 cell tumors or patient-derived xenograft tumors, and blood analysis (including mass spectrometry) was performed. FTY720 and pro-FTY inhibited the survival of all breast cancer cell lines, including multidrug-resistant cells resistant to paclitaxel or doxorubicin. Unlike pro-FTY, FTY720 inhibited the survival of normal breast cell lines, suggesting that pro-FTY does not affect normal breast cells. Pro-FTY showed reproducible activity against multidrug-resistant PDOs, whereas paclitaxel and doxorubicin did not. Mass spectrometric analysis of pro-FTY-treated mice showed that FTY720 accumulated in tumors but was barely detectable in blood. Importantly, lymphocytopenia occurred in FTY720-treated mice but not in pro-FTY-treated mice. Furthermore, intravenous pro-FTY treatment significantly suppressed tumor growth in mice bearing patient-derived xenograft tumors generated from multidrug-resistant PDOs. In conclusion, pro-FTY inhibited breast cancer, including multidrug-resistant breast cancer, while avoiding lymphocytopenia, highlighting its clinical potential.

To evaluate the efficacy and toxicity of consolidation chemotherapy (C-CT) following concurrent cisplatin chemotherapy combined with intensity-modulated radiotherapy (IMRT) in patients with early-stage cervical cancer who present high-risk factors (HRFs).

We evaluated the growth-inhibitory effects of three γ-butyrolactam (γ-lactam) derivatives (compounds 5, 6, and 8) on human breast cancer cells (MCF-7) and in a xenografted chick model. Growth inhibition was assessed using MTT assays and flow cytometry for compounds 5, 6, and 8, followed by Western blot analysis to examine the expression levels of cell cycle-associated proteins. Chick embryos were utilized as a xenograft model for further validation. The results revealed that compound 8 exhibited relatively low toxicity among the tested compounds. Western blot analysis suggested that compounds 5, 6, and 8 may be involved in the EGFR and P53 signaling pathways. In the xenograft model, compound 8 significantly inhibited MCF-7 tumor growth in chick embryos (tumor size in control group: 1.97 ± 0.69 mm, n = 15; compound 8-treated group: 1.20 ± 0.37 mm, n = 15). These findings suggest that compound 8 effectively inhibits MCF-7 growth with minimal toxicity, warranting further investigation in mammalian models.

A series of six novel cyanopyridine derivatives bearing a 1,3,4-oxadiazole ring have been synthesized and characterized by FTIR, 13C NMR, 1H NMR, and elemental analysis. DFT calculations were carried out to determine their molecular geometries, electronic properties, and chemical reactivity. Their cytotoxicity has been evaluated against MCF-7 and CaCo-2 human cancer cell lines using the MTT assay. Most compounds displayed poor cytotoxic activity against the MCF-7 cell line except for compound 4e, which showed potent activity with IC50 = 8.352 µM. However, the CaCo-2 cell line was highly sensitive toward most tested compounds with an IC50 range from 2.612 µM to 8.394 µM except for compound 4 d. Molecular docking studies targeting human topoisomerase-IIβ revealed that all compounds exhibited excellent binding affinity within the enzyme's active site, with binding energies ranging from -7.33 to -8.28 kcal/mol. These findings suggest a potential anticancer mechanism underlying the observed cytotoxic activities. All tested compounds revealed low antioxidant activity in the DPPH assay. However, compounds 5b and 5 d presented moderate metal chelating activity. These findings underscore the potential anticancer properties of the synthesized cyanopyridine derivatives.

Menin inhibitors, which target the KMT2A-menin protein-protein interaction to inhibit blasts proliferation and induce differentiation, have demonstrated potential effects on acute leukemia subtypes characterized by overexpression of HOXA gene cluster and MEIS1 (including KMT2A rearrangements, NPM1 mutations, NUP98 rearrangements and other genetic alterations). Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.

Adult T-cell leukemia/lymphoma (ATLL) has low overall survival, underscoring the need for the development of novel approaches. Present study aimed to investigate anti-proliferative effects of entinostat and its newly synthesized analogs on ATLL cells. Computational analyses were conducted to identify the potential molecular targets of entinostat, and construct a protein-protein interaction network. Then, enrichment analyses were performed, and the expression of CDK4 was assessed in MT-2 cells. Molecular docking and dynamics simulations were carried out to predict the interactions of entinostat and its novel analogs with target proteins. For in vitro studies, at first quinoline-based benzamide derivatives were synthesized. Then, MT-2 and normal cells were treated and their proliferation was evaluated by alamarBlue assay. Finally, flow cytometry was performed, and the expression of candidate genes was assessed by real-time PCR. Exploring potential targets of entinostat and pathogenic targets of ATLL revealed 51 overlapping molecules including CDK4. Volcano plot revealed over expression of CDK4 in MT-2 cells. Favorable and stable binding of entinostat and its analogs with the activation loop of CDK4 and the CDK-binding site of cyclin D1 was confirmed. Experimental studies revealed anti-proliferative effects of entinostat and analogs on MT-2 cells, confirmed by flow cytometry analysis and alterations in the expression of BAX, CCND1, and BCL-2. Present findings pave the way for the development of new drugs against ATLL, and provide evidence that justifies further preclinical evaluations of entinostat and its novel analogs.

Microtubules and nuclear transmembrane SUN1/2 proteins promote the mobility of DNA Double Strand Breaks (DSBs) induced by ionizing radiation and the misrepair of one-ended DSBs induced in BRCA1-deficient cells by Poly(ADP-ribose) polymerase inhibitors (PARPi). However, whether microtubules promote aberrant DSBs repair by altering the nuclear structure and whether the nuclear structure itself plays a role in these processes is still unclear. Here we show that microtubule-dependent DSBs mobility in BRCA1-deficient cells after PARPi treatment is associated with nuclear envelope (NE) invaginations. Furthermore, increasing NE invaginations by Lmna deletion or inhibition of sphingolipid synthesis increases DSBs mobility, chromosomal aberrations, and PARPi cytotoxicity in BRCA1-deficient cells. These findings reveal a functional connection between the NE and DSB repair and suggest that drugs increasing NE deformability will enhance PARPi therapy efficacy in BRCA1-deficient cancers.

Linperlisib is a highly selective small-molecule inhibitor of phosphatidylinositol-3-kinase delta for the treatment of relapsed/refractory follicular lymphoma.

Last few decades, extensive research efforts have been dedicated to uncovering novel cancer treatments. Among the most vital targets in this pursuit are matrix metalloproteinases (MMPs), enzymes integral to the progression and spread of cancer. Their role in tumor development and metastasis positions MMPs as key players in cancer pathogenesis, offering promising avenues for therapeutic intervention. Specifically, MMP-2 and MMP-9 have emerged as promising targets in cancer treatment based on their critical roles in cell invasion, angiogenesis, immune evasion, and metastasis. Studies indicate the potential of plant-derived natural products as anticancer agents through the regulation of MMP activity. Among various phytochemicals, flavonoids are reported to exhibit inhibitory activities against MMPs and antioxidant properties that present them as candidates for anticancer molecules. In this study, the potential of flavonoids as anticancer agents was explored by investigating the effects of flavonoids on (i) cancer cell viability and migration, (ii) enzymatic activity and cellular expression of MMP-2/9, and (iii) the MAPK signaling pathway. Docking simulation data regarding the interactions between MMP-2/9 and selected flavonoids provide an in-depth look at the potential mechanisms through which these molecules suppress the enzymatic activities of MMPs. Select flavonoids exhibited notable efficacy in suppressing cell proliferation and migration in A549 cells, which may be a consequence of their ability to attenuate MMP activity and expression through the suppression of the MAPK signaling pathway. These observations demonstrate the prospect of flavonoids as a naturally occurring molecular framework for the development of novel anticancer therapeutics.

Atezolizumab is an immune checkpoint inhibitor that targets PDL-1 (programmed death ligand-1) on the tumour cells and inactivates it. The addition of this drug to chemotherapy has led to survival benefits in the treatment of small cell lung cancer-extensive stage (SCLC-ES). However, these excellent outcomes may be marred by the development of immune-mediated adverse events (irAEs). The pathophysiology of these irAEs is not well defined, and as a result, they are less understood as an entity. In addition to this, the highly non-specific presentation and unawareness among treating physicians may lead to delays in diagnosis and subsequently affect patient outcomes. Immunotherapy-induced myositis is one such rare irAE.Herein, we present a case of a male in his early 70 s undergoing treatment for SCLC-ES, who initially presented with non-specific symptoms and grade four transaminitis and was subsequently diagnosed with atezolizumab-related myositis after comprehensive evaluation. The patient was managed successfully and has an ongoing response more than 6 months after stopping immunotherapy and 18 months since initial diagnosis. This case report aims to address the knowledge gap regarding this irAE with insights on diagnosis and management.

We report a case of a male in his 60s with a past medical history of glioblastoma status post chemoradiotherapy and surgical resection. He had completed neoadjuvant temozolomide and was 26 days post-chemotherapy on presentation. He presented with fever, weakness, and confusion. Further evaluation revealed cytomegalovirus (CMV) ventriculoencephaltis. He was started on valganciclovir, but his hospital course was complicated by a pulmonary embolism. Repeat imaging showed tumor progression, and he was a poor surgical candidate. This case highlights the complexities of managing patients with opportunistic infections post-chemotherapy. It adds to the growing literature of disseminated, invasive, and often lethal CMV infections in non-HIV patients post-use of temozolomide. We urge the need for vigilant monitoring and consideration of prophylactic measures in individuals deemed at risk for invasive CMV.

Nilotinib, a second generation tyrosine kinase inhibitor, has remarkably improved outcomes in patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia by targeting BCR-ABL1 fusion protein. Despite the safety and efficacy of these agents, adverse side effects can occur due to unintended inhibition of off-target kinases. While the clinical ramifications of serosal inflammation - including pleural and pericardial effusions - have been a common occurrence in patients on older tyrosine kinase inhibitors (TKI), the effect of nilotinib causing pericardial effusion is rare. This case report highlights a rare occurrence of pericardial effusion while being treated with nilotinib for chronic myeloid leukemia.

Wolf isotopic response refers to a new skin disorder manifesting in the area of a previous skin lesion that has healed. A variety of disease processes and dermatoses have been described that evoke an isotopic response. We report a man with metastatic hepatocellular carcinoma who received palliative radiation and later experienced a pembrolizumab-induced lichenoid dermatitis at the same site of radiation, representing a cutaneous immune-related adverse event displaying an isotopic response.