Malignant Pleural Mesothelioma (MPM) is the most prevalent type of Mesothelioma and currently has no effective treatment options. This underscores the urgent need to explore new therapeutic agents and innovative strategies. Phenolic acids are significant natural compounds recognised for their effectiveness in treating various diseases, including cancer. This study evaluates the anti-carcinogenic properties of Cinnamic acid (CINN) and its derivative Caffeic acid (CA) in both MPM and non-cancerous mesothelial cells. Results show that CA exhibited greater efficiency than CINN in reducing cancer cell survival. This enhanced efficacy is primarily attributed to CA's higher selectivity index and its ability to inhibit proliferation at lower concentrations. Consequently, further analysis was conducted using CA. The subsequent findings revealed that CA suppressed proliferative markers, Ki67 and PCNA, inhibited colony formation and wound healing in MM cells. Experiments also exposed that it suppresses the phosphorylation of ERK1/2 and AKT proteins in a concentration-dependent manner, while the phosphorylation of STAT3 remains unaffected. The pattern of protein phosphorylation and expression suppression by CA in 3D cells resembles that in 2D cells, although it occurred at higher concentrations. Additionally, CA significantly enhanced the expression of p53-regulated proteins p21 and p27, resulting in G2/M arrest in both SPC111 and SPC212 cell lines. Moreover, elevated concentrations of CA were associated with an increased number of dead cells, as demonstrated by DAPI/PI and AO/EtBr fluorescence staining. The increased Bax/Bcl-2 protein ratio, and BH3-only proteins (Bik and PUMA) and the cleavage of caspase-3 indicated that CA induces mitochondrial apoptosis. Our research with MM cells and three-dimensional micro-tumours suggests that CA may be a promising alternative for future MM therapies. However, it is vital to conduct high-throughput in vivo studies to elucidate further the potential importance of CA in treating this devastating disease.

Cancer is a significant public health problem worldwide, and its morbidity and mortality are challenging to improve, which is an important obstacle to prolonging life expectancy. Cytotoxic drugs have been used in anti-cancer therapy since the 1940s. They play an important role in tumor therapy. However, drug resistance and systemic toxicity often limit its application. Combination or synergistic chemotherapy can promote therapeutic effects and reduce toxicity. Quercetin (QUE) is a natural flavonoid widely found in fruits and vegetables. It has anti-cancer, anti-inflammatory, antioxidant, and neuroprotective properties. An increasing number of studies have found that the combination of QUE and chemotherapy drugs has a chemosensitization effect. To a certain extent, it can inhibit the side effects of chemotherapeutic drugs, such as nephrotoxicity, cardiotoxicity, reproductive toxicity, and neurotoxicity, which has attracted great attention. The immune system plays a significant role in tumor development. Notably, several studies have revealed that QUE plays an immunomodulatory role by promoting the differentiation of anti-cancer immune cells and inhibiting immune checkpoint expression. In conclusion, current studies have emphasized the potential of QUE in chemosensitization, reduction of toxic side effects, and enhancement of the anti-cancer immune response. However, more preclinical and clinical cohort studies are needed to determine QUE's efficacy, mechanism, optimal formulation, and long-term effects in synergistic chemotherapy and immunomodulatory effects.

Nivolumab, a human immunoglobulin IgG4 monoclonal antibody targeting PD-1 receptor, received initial FDA approval in 2014 for treating unresectable or metastatic malignant melanoma (MM), followed by approval for metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) in 2015. With expanding clinical applications of nivolumab, comprehensive evaluation of its safety profile in real-world healthcare settings becomes increasingly crucial.

The therapeutic efficacy of nanomedicine in oncology is predicated on its capacity to enhance drug uptake by cells and control drug release. While targeted nanomedicines are highly regarded for their potential, they are not spared from issues of colloidal instability and uncontrolled drug release.

The therapeutic efficacy of intravesical agents for bladder cancer (BCa) is frequently constrained by their clearance via urine flushing and periodic bladder emptying, as well as the absence of tumor-targeting capabilities. Consequently, an effective drug delivery system must possess both tumor-targeting and adhesion properties to overcome these limitations.

Immune checkpoint inhibitors (ICIs) have demonstrated significant therapeutic benefits but are also associated with skin-related adverse reactions. The specific characteristics of severe adverse reactions caused by ICIs remain unclear.

Cancer is among the leading causes of death worldwide, with projections indicating that it will claim 35 million lives by the year 2050. Conventional therapies, such as chemotherapy and immune modulation, have reduced cancer mortality to some extent; however, they have limited efficacy due to their broad mode of action, often resulting in cytotoxic effects on normal cells along with the malignant tissues, ultimately limiting their overall optimal therapeutic efficacy outcomes.Rapid advances in nanotechnology and an evolving understanding of cancer mechanisms have propelled the development of a diverse array of nanocarriers to vanquish the hurdles in achieving sophisticated drug delivery with reduced off-target toxicity. Nanoformulations can deliver the anti-cancer agents precisely to the tumor cell by integrating a multitarget approach that allows for tissue-, cell-, or organelle-specific delivery and internalization. Despite the immense interest and unmatched advancements in modern oncology equipped with nanomedicines, only a few nanoformulations have successfully translated into clinical settings. A major reason behind this shortcoming is the lack of a rationale design incorporating smart, responsive targeting features, leading to a compromised therapeutic window due to inefficient internalization or erroneous intracellular localization with unsuccessful payload release. This review aims to summarize the recent perspective of nanomedicine and its translation to clinical practice, with a particular focus on the evolution of strategies used in tumor targeting from traditional EPR-based passive mechanisms to advanced active and multi-stage approaches. We highlight the coupling of organelle-specific and stimuli-responsive nanocarriers, discuss the potential of biomimetic and cell-mediated delivery systems, and also shed light on technologies such as microfluidics, tumor-on-chip models, and AI-assisted synthesis. Finally, this review explores translational hurdles ranging from biological and manufacturing challenges to regulatory bottlenecks and outlines how innovative modeling systems and engineering solutions can bridge the gap from bench to bedside in cancer nanotherapeutics.

Nasopharyngeal carcinoma (NPC) is one of the most prevalent cancers in the head and neck region. The development of innovative therapies that are effective at eliminating tumors while minimizing damage to surrounding normal tissues due to postoperative complications is crucial. To solve this problem, a gelatin-sodium alginate (Gel-SA) hydrogel containing bismuth selenide nanosheets (Bi2Se3 NSs) has been developed, which introduces a "switch" of near-infrared (NIR) light for photodynamic therapy (PDT) and photothermal therapy (PTT) to significantly increase the level of oxidative stress while inducing ferroptosis and apoptosis to synergistically treat tumors. Once the treatment of the tumor has been completed, NSs remove a large number of free radicals left by NIR irradiation because of their excellent anti-inflammatory performance and combine with the rich nutrients in Gel-SA to protect and repair the tissues around the tumor. Combining Bi2Se3 NSs and Gel-SA is an effective solution for treating NPC, as it ablates tumors while protecting surrounding tissues.

The incidence of cancer diagnosed during pregnancy is increasing, but data relating to perinatal outcomes for infants exposed to systemic cancer treatment in utero remain limited. This systematic review and meta-analysis aimed to synthesise evidence from the available literature to investigate whether perinatal outcomes for babies born to women with gestational cancer differ based on whether they are exposed to systemic cancer treatment in utero.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the gold standard treatment for neovascular age-related macular degeneration (nAMD) which is responsible for central vision loss. This results in loss of quality of life, comparably severe to having coronary artery disease or cancer. New anti-VEGF agents need to address issues of potency and durability as existing agents tend to lose their effect after 1 month thus, requiring multiple injections at close intervals. Brolucizumab is one of the latest anti-VEGF agents clinically proven to treat nAMD after on-label agents namely, ranibizumab and aflibercept. Several clinical trials were conducted on Brolucizumab to ensure its safety and efficiency before it is approved to be used as treatment. Brolucizumab maintains and improves retinal edema in nAMD leading to improved vision with longer intervals possible between injections. However, it also has a risk of intraocular inflammation. This review summarizes the evidence for brolucizumab in the treatment of nAMD.

Fluoroquinolones, such as levofloxacin (LVX), are extended-spectrum drugs used for the treatment of bacterial infections. Several fluoroquinolone derivatives have shown promising antibacterial and anticancer activities. Our group has earlier synthesized and investigated thionated LVX analogs, compounds 2 and 3, on A549 (non-small cell lung cancer) cell line and showed promising anticancer activity. The mechanism of cytotoxicity may be, in part, via aldehyde dehydrogenase enzyme inhibition and antioxidation. In this study, compounds 2 and 3 were evaluated on prostate (PC-3), breast (MCF7), colorectal (Caco-2), and small cell lung cancer (H69 and H69AR) cell lines.

Targeting immune checkpoint pathways to evoke an immune response against tumors has revolutionized clinical oncology over the last decade. Antibodies that block the PD-1/PD-L1 pathway have demonstrated effective antitumor activity in cancer patients and are approved for treatment of several different types of cancer. However, many patients do not experience durable beneficial clinical responses. The ability to predict response to immunotherapy is a clinical need with immediate implications on the optimization of oncologic treatments. In this work we developed and tested the ability of an Agent-Based Model (ABM) to predict the ex vivo immune response of memory T cells to anti-PD-L1 blocking antibody, based on personalized immune-phenotypes. We performed mixed lymphocyte reaction (MLR) experiments on blood samples of healthy volunteers to model the dose-response kinetics of the immune response to anti-PD-L1 antibody. Additionally, immunophenotype of peripheral lymphocyte and monocyte populations was used for modeling and prediction. In silico MLR experiments were conducted using the ABM-based Cell Studio Platform, and the results of ex vivo vs. in silico experiments were compared. Our ABM accurately recapitulates MLR-derived immune responses, achieving >80% predictive accuracy. Notably, given the relatively small cohort tested, such results are typically impossible to model with methods based solely on statistical or data-driven approaches. Importantly, the use of this modeling strategy not only predicts the outcome of the immune response, but also provides insights into the exact biological parameters and related cellular mechanisms that lead to differential immune response.

Despite Garlic's (Allium. sativum) long-standing reputation for therapeutic properties, comprehensive studies on Tunisian garlic are lacking. This study aims to evaluate different Tunisian A. sativum extracts rich in bioactive compounds (phenolic acids, flavonoids, and vitamins), exploring their potential bioactivities (antifungal, antioxidant, and cytotoxic). A. sativum samples underwent hexane, ethyl acetate, methanol, and water-based extractions. LC-MS quantification assessed bioactive compounds. Antioxidant activity was determined via the DPPH assay, antifungal effects were evaluated against Aspergillus spp., and cytotoxic effects were assessed using the MTT assay on U266 human multiple myeloma and MDA-MB-231 metastatic breast cancer cell lines. The aqueous extract exhibited the highest phenolic acid content (96.25 mg/kg fw) and the most water-soluble vitamins (14.69 mg/kg fw). In contrast, the methanol extract was richest in flavonoids, while the ethyl acetate extract had the highest concentration of fat-soluble vitamins (20.21 mg/kg fw). Both aqueous and methanolic extracts demonstrated potent antioxidant activity. The aqueous extract exhibited the strongest antifungal activity (MIC: 1.5 mg/mL for A. flavus and 3 mg/mL for A. niger). Furthermore, the ethyl acetate extract showed remarkable cytotoxic effects against cancer cell lines, indicating its potential as an effective agent against metastatic breast cancer and refractory multiple myeloma. A. sativum emerges as a functional food source with antioxidant, antifungal, and cytotoxic activities, particularly against multiple myeloma. While this study provides a strong foundation for further exploration, additional research is needed to identify active compounds, elucidate mechanisms, and assess therapeutic potential.

Although the presence of Kirsten murine sarcoma virus (KRAS) mutations predicts a failure of non-small cell carcinoma (NSCLC) patients to benefit from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy it may be more sensitive to programmed combination therapy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors + anti-angiogenesis. Recent treatment guidelines and clinical studies related to adenocarcinoma in NSCLC have indicated that in patients with inoperable stage IV lung adenocarcinoma, immune checkpoint inhibitors in combination with anti-angiogenic drugs may exert a synergistic effect and significantly improve the efficacy of near-term treatment, but quantification and long-term follow-up of specific clinical indicators are still lacking. No previous cases of long-term good results with camrelizumab combined with anti-angiogenic agents for KRAS-mutated NSCLC have been described.

Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ-specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy.

Glioblastoma (GBM) is a malignant tumor that currently still faces challenges for a complete cure. Although GBM treatment has made great progress, the prognosis of patients is still poor due to interference of various factors in treatment such as the blood-brain barrier (BBB), grade malignancy, intra- and intertumor heterogeneity, drug resistance, and poor targeting of anti-tumor drugs. In recent years, with marked advances in nanotechnology, different types of nanodrug delivery systems have been developed and have been considered as a promising therapeutic measure to gradually overcome chemotherapy resistance and improve tumor targeting. Carbon dots (CDs), as a new type of therapeutic NP, have become a research hotspot of concern for many researchers in recent years. NPs based on CDs have high modifiability and functionalization, allowing for covalent binding with chemotherapy drugs, genes, immune cells and photosensitizers, effectively targeting tumor cells and reducing peripheral cytotoxicity. However, at present, CDs are still in the basic research stage or the preclinical exploratory research stage, and has not yet entered the clinical trial stage or the implementation and application stage. Here, we review the fundamental principles of CDs in the broader field of nanotechnology, their development history, classification, synthesis, and potential for tumor treatment. Especially in the treatment of cancer, CDs can not only participate in photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy, and chemotherapy, but also in multi-modal combination therapy. Here, we hope to provide some insights for further research.

The monoclonal antibodies consist of an innovative form of immunotherapy, capable of defeating several diseases, such as cancer. It is an emergent and important theme, that advances evaluation, challenges, and future perspectives with high relevance to identify gaps in recent studies and to consolidate this general theme in only one research. Its action in Chronic and Acute Lymphoid Leukemia has been evaluated in several clinical trials, which were selected between 2022 and 2023, in order to understand better the monoclonal antibodies that were most studied. The biopharmaceutical compounds Ibrutinib, Obinutuzumab, Rituximab, Venetoclax, and Inotuzumab Ozogamicin were the ones that most appeared in the most recent publications, indicating the importance of amplifying the studies. The action mechanisms that are used imply that their combined use has more success in the disease remission, showing a lower recurrence, adverse effects, and toxicity. Besides the adverse effects and overwhelming prices of the treatment, these immunotherapies results are promising, amplifying the survival rates, improving the patient's life quality, and resulting in a precision medicine, aiming a custom treatment. The future perspectives on this therapy consist of its application in the public health system, with patients being able to be submitted to this treatment without any costs and receive a better life quality.

Apatinib has been reported to be a promising treatment for sorafenib-resistant hepatocellular carcinoma (HCC) patients. However, the underlying mechanism remains ambiguous. The study aimed to explore the efficacy of apatinib in sorafenib-resistant HCC and the underlying mechanism both in vitro and in vivo.

The cell cycle is a tightly coupled series of events that enable cells to grow and proliferate. Cyclin-dependent kinases (CDKs) play crucial roles in the cell cycle by enabling cells to transition between different phases when they are activated. Cell cycle proteins enhance the activity of CDKs, while natural CDK inhibitors (CDKIs) suppress them. The cell cycle continues in cycles under normal conditions, but when conditions change, cells halt or terminate the cell cycle. Tumors are tissues that grow out of control, and the mechanisms of various types of tumors are different; however, almost all tumor cells share several common characteristics, including proliferation, prevention of apoptosis and genomic instability. Cellular division is essential in the progression of cancer. A key characteristic of cancer is the uncontrolled growth of tumor cells, which is due to the erratic behavior of several proteins during the cell cycle. Therefore, cell cycle regulators are considered attractive targets for the treatment of cancer. The present analysis highlights proteins that play a direct role in controlling the tumor cell cycle, such as CDKs, and provides a brief overview of checkpoint kinases. The present review also discusses how cell cycle proteins contribute to cancer and describes some of the antitumor drugs that are being researched.

Triphenylphosphine (TPP) and Doxorubicin (DOX) were conjugated to obtain Triphenylphosphine-Doxorubicin (TPP-DOX), which was applied in tumor cells for enhancement of DOX in mitochondria targeting. The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.