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.

Rapid access to safe and effective oncological therapies is crucial. In recent years, many expensive drugs have been commercialized, making it essential to prioritize those with significant clinical benefits. For this purpose, the European Society for Medical Oncology (ESMO) introduced the ESMO-MCBS (Magnitude of Clinical Benefit Scale), which assigns a score to quantify the clinical benefit of treatments. This study aims to evaluate whether there is a correlation between the ESMO-MCBS score and drug access times in Italy.

Disulfidptosis, a form of programmed cell death triggered by disulfide stress, holds promise for antimetastatic strategies by promoting cytoskeletal collapse, while no relevant applied study was reported. Herein, we develop a disulfide stress inducer for antitumor metastasis by nitroimidazole-grafted poly(sodium lipoate) nanoparticles (NI@PSL). Upon thiol-mediated cellular uptake, NI@PSL degraded into dihydrolipoic acid (DHLA) and exposed grafted nitroimidazole (NI) in response to glutathione (GSH). DHLA formed aberrant disulfide bonds with cytoskeletal cysteine thiols. NI moieties were reduced to aminoimidazole by hypoxia-activated nitroreductase, resulting in nicotinamide adenine dinucleotide phosphate (NADPH) depletion. This redox imbalance prevented the reduction of intercytoskeletal disulfide bonds, leading to irreversible cytoskeletal collapse and subsequent metastasis inhibition. In vitro assays demonstrated that NI@PSL decreased the migration and invasion rates of highly metastatic B16F10 cells to 12.8 and 7.0%, respectively. In the B16F10 tumor-bearing mice model, NI@PSL nearly eliminated lung and liver metastatic foci. These results provide a strong basis for using disulfide stress to combat tumor metastasis.

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.

To investigate the impact of Forkhead box Q1 (FOXQ1) expression on platinum-based chemoresistance in colorectal cancer (CRC) cells, and to examine the regulatory function of FOXQ1 on Sirtuin 1 (SIRT1) protein expression and P53 protein deacetylation levels during the DNA damage response (DDR).

Lung cancer has the second-highest incidence rate after breast cancer and remains the leading cause of cancer-related mortality. The 1-year survival rate for lung cancer patients is below 50%, highlighting the urgent need for novel therapeutic strategies and drug development. Phytochemicals and their derivatives have been widely explored for their anticancer properties, serving as chemotherapeutic agents against various types of cancer. One of these herbal compounds, berberine (BBR), a quaternary isoquinoline alkaloid, has shown significant promise in preclinical studies and is currently undergoing clinical trials for cancer treatment. BBR exhibits diverse biological activities, contributing to its anticancer potential, including antioxidant, antidiarrheal, antidiabetic, antimicrobial, and so on. However, despite its multifunctional therapeutic potential, BBR faces several limitations, hindering its clinical application, like poor bioavailability, low tissue uptake, a short plasma half-life, and rapid metabolic elimination. To address these challenges, various targeted drug delivery approaches have been developed to improve its efficacy. This review aims to provide a comprehensive overview of drug delivery strategies designed to encapsulate BBR for enhanced lung cancer therapy, highlighting the most recent advancements in the field. Moreover, the molecular structure of BBR and the biological pathways it targets to inhibit lung cancer progression are discussed in detail. Finally, BBR-encapsulated nanocarriers specifically developed for lung cancer therapy are evaluated in terms of their benefits, limitations, and overall therapeutic potential.

Despite extensive research, the topic of anti-PD-L1 small-molecule inhibitors remains elusive. Herein, we report the design, synthesis, and bioevaluation of a series of small molecule PD-L1 inhibitors via optimization of the solvent-interaction region. Among them, compound GJ19 showed the most potent anti-PD-L1 effects with an IC50 of 32.06 nM in the HTRF (homogenous time-resolved fluorescence) assay, better than BMS-202 (IC50 = 62.1 nM). In addition, the SPR (surface plasmon resonance) assay revealed that GJ19 can effectively bind to human/murine PD-L1 protein with KD values of 171 and 290 nM, respectively. Furthermore, GJ19 concentration-dependently promoted HepG2 cell mortality in a co-culture model of HepG2/hPD-L1 and Jurkat T/hPD-1 cells. In the in vivo efficacy studies, GJ19 (intraperitoneal injection, 15 mg/kg) effectively suppressed tumor growth with a TGI of 56.8% in a B16-F10 melanoma mouse model by activating antitumor immunity. In conclusion, GJ19 represents a potential small molecule inhibitor of PD-L1, deserving further investigation for tumor immunotherapy.

Androgen-independent prostate cancers, correlated with heightened aggressiveness and poor prognosis, are caused by mutations or deletions in the androgen receptor (AR) or the expression of truncated variants of AR that are constitutively activated. Currently, drugs and drug candidates against AR target the steroid-binding domain to antagonize or degrade AR. However, these compounds cannot therapeutically access largely intrinsically disordered truncated splice variants of AR, such as AR-V7, which only possess the N-terminal transactivation domain and DNA-binding domain and are missing the ligand-binding domain. Targeting intrinsically disordered regions within transcription factors has remained challenging and is considered "undruggable". Herein, we leverage a cysteine-reactive covalent ligand library in a cellular screen to identify the degraders of AR and AR-V7 in androgen-independent prostate cancer cells. We identified a covalent compound, EN1441, that selectively degrades AR and AR-V7 in a proteasome-dependent manner through direct covalent targeting of intrinsically disordered cysteine C125 in the N-terminal transactivation domain of AR and AR-V7. EN1441 causes significant and selective destabilization of AR and AR-V7, leading to the aggregation of AR/AR-V7 and subsequent proteasome-mediated degradation. Consistent with targeting both AR and AR-V7, we find that EN1441 completely inhibits total AR transcriptional activity in androgen-independent prostate cancer cells expressing both AR and AR-V7 compared with AR antagonists or degraders that only target the ligand-binding domain of full-length AR, such as enzalutamide and ARV-110. Our results put forth a pathfinder molecule EN1441 that targets an intrinsically disordered cysteine within AR to destabilize, degrade, and inhibit both AR and AR-V7 in androgen-independent prostate cancer cells and highlights the utility of covalent ligand discovery approaches in directly targeting, destabilizing, inhibiting, and degrading classically undruggable transcription factor targets.

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.

Glioblastoma (GB) is a highly aggressive brain tumor with poor prognosis due to its invasiveness and resistance to conventional therapies, necessitating advanced drug delivery systems to enhance treatment efficacy and reduce toxicity. This study aims to develop and evaluate dual-responsive magnetic and pH-sensitive beads for controlled cisplatin delivery to glioblastoma cell lines, addressing challenges in targeted therapy. Cobalt ferrite (CoFe2O4) nanoparticles were synthesized via a green co-precipitation method using clove extract as an alkalizing and stabilizing agent. These nanoparticles were incorporated into sodium alginate beads with cisplatin, cross-linked by Ca2+ ions. Beads were characterized using FTIR, XRD, SEM, and VSM. Swelling behavior, encapsulation efficiency, and in vitro drug release were assessed at pH 1.2 and 7.4, with and without a magnetic field. Cytotoxicity was evaluated via MTT assay on T98, A172, and L929 cell lines. The beads exhibited pH-dependent swelling, with maximum absorption at pH 7.4. Drug release was significantly enhanced under a 100 Hz magnetic field, achieving 70.2% cisplatin release in 80 min for CisB-4 beads. MTT assays demonstrated significant cytotoxicity against T98 and A172 cells (p < 0.05 to p < 0.0001), with minimal toxicity to normal L929 cells. These dual-responsive beads offer a promising platform for targeted cisplatin delivery in glioblastoma, with pH and magnetic field-mediated control, potentially improving therapeutic outcomes while minimizing systemic toxicity.

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.

Glioblastoma is a rapidly growing form of brain tumour originating from the supportive tissues present in the brain or spinal cord. The conventional therapeutic options include the use of alkylating agents, radiation and surgical procedures, that exhibits numerous limitations. The considerably less survival rate, very high incidence of recurrence and lack of effective therapeutic options has made the disease as the most lethal brain cancer. Being widely investigated, nanocarriers assure efficacy in brain targeting. Nano-based systems also hold the edge of higher encapsulation efficiency, ability to encapsulate anticancer therapeutics and effective blood brain barrier (BBB) penetration ability has been proven as one of the most successful means of delivering therapeutic agents in brain interstitial. The extreme biocompatible and biodegradable features of chitosan (CS) have been advantageous in combination with its easy fabrication and modifiable physicochemical behaviour. CS has been extensively investigated in the synthesis of nano-systems for brain targeting of drugs. The mucoadhesive behaviour of CS, cationic nature, and its ability to conjugate with various ligands helps in effective targeting of glioblastoma. This review specifically focuses on the fabrication of various CS-based nanocarriers for glioblastoma therapy, alongside describing its suitability and reflecting the recent research outcomes in glioblastoma therapy.

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.