Anticancer Treatment Research Articles

P20-1 Photodynamic-controllable smart delivery of combined PARP inhibitor with natural nanoparticles for anticancer treatment

P20-1 Photodynamic-controllable smart delivery of combined PARP inhibitor with natural nanoparticles for anticancer treatment

When cancer patients encountered COVID-19: clinical characteristics and outcome in China.

Cancer patients were more likely to be affected by the coronavirus disease 2019 (COVID-19) pandemic. Therefore, we analyzed the clinical characteristics and outcomes in cancer patients who were infected with COVID-19 to determine if they were more vulnerable to COVID-19 than non-cancer patients. This retrospective study involved 150 cancer patients and 300 non-cancer patients with a laboratory-confirmed diagnosis of COVID-19 at the Cancer Hospital of the Chinese Academy of Medical Sciences, at the end of 2022. Multivariable analysis was carried out on the factors associated with COVID-19 severity in cancer patients. Compared to the non-cancer group, the cancer group saw a notably higher number of hospitalizations and fatalities. Multivariate analysis showed that COVID-19 severity was correlated with male gender (OR: 5.60, 95% CI, 1.89-16.57), and recovery duration was longer than 10 days (OR: 3.19, 95% CI, 1.09-9.32) in the cancer group. However, the severity of COVID-19 was not made worse by the administration of systemic anticancer treatments prior to the outbreak. During the COVID-19 Omicron epidemic, there seemed to be some association between various antitumor therapies, treatment intervals, and COVID-19 severity. The findings of this study can potentially help allay cancer patients` fears regarding COVID-19 infection and enable them to continue with crucial therapeutic processes for the treatment of cancer.

Palliative and End of Life Care: An Important Component of Supportive Oncology.

Palliative care, an integral component of supportive oncology, enhances the quality of life for patients living with cancer. Whilst palliative care has historically been synonymous with the provision of care at the end of life, it is increasingly playing a role earlier in a patient's cancer journey; frequently in conjunction with administration of anticancer treatment. Although early integration has been shown to improve patient outcomes, service development remains in its infancy and consideration of challenges bears relevance. Addressing issues pertaining to resource allocation in addition to adequate training of staff will aid to ensure the provision of care that aligns with the goals and priorities of patients. This review presents the role of early palliative care within the realm of supportive oncology with respect to the evidence of benefit and ethical, clinical and practical considerations. Relevant papers have been chosen for inclusion on the basis of clinical relevance, timeliness and relevance to cancer patients and clinical teams involved in their care.

Application of Gold Nanoparticles for Improvement of Electroporation-Assisted Drug Delivery and Bleomycin Electrochemotherapy.

Background/Objectives: Electrochemotherapy (ECT) is a safe and efficient method of targeted drug delivery using pulsed electric fields (PEF), one that is based on the phenomenon of electroporation. However, the problems of electric field homogeneity within a tumor can cause a diminishing of the treatment efficacy, resulting only in partial response to the procedure. This work used gold nano-particles for electric field amplification, introducing the capability to improve available elec-trochemotherapy methods and solve problems associated with field non-homogeneity. Methods: We characterized the potential use of gold nanoparticles of 13 nm diameter (AuNPs: 13 nm) in combination with microsecond (0.6-1.5 kV/cm × 100 μs × 8 (1 Hz)) and nanosecond (6 kV/cm × 300-700 ns × 100 (1, 10, 100 kHz and 1 MHz)) electric field pulses. Finally, we tested the most prominent protocols (microsecond and nanosecond) in the context of bleomycin-based electrochemotherapy (4T1 mammary cancer cell line). Results: In the nano-pulse range, the synergistic effects (improved permeabilization and electrotransfer) were profound, with increased pulse burst frequency. Addi-tionally, AuNPs not only reduced the permeabilization thresholds but also affected pore resealing. It was shown that a saturated cytotoxic response with AuNPs can be triggered at significantly lower electric fields and that the AuNPs themselves are non-toxic for the cells either separately or in combination with bleomycin. Conclusions: The used electric fields are considered sub-threshold and/or not applicable for electrochemotherapy, however, when combined with AuNPs results in successful ECT, indicating the methodology's prospective applicability as an anticancer treatment method.

Bibliometric Analysis of Pyrimidine Compounds with Anti-cancer Activity: Research Trends from 2015 to 2023

Cancer remains one of the most pervasive diseases in the world, globally, leading to millions of fatalities annually. Currently, numerous anti-cancer treatments are available to address the various types of cancer. Pyrimidine, a class of heterocyclic nitrogenous compounds, holds substantial promise in anti-cancer drug development due to its structural similarity to the nucleotide base pairs found in DNA and RNA. This work aimed to conduct a bibliometric analysis of studies on pyrimidine compounds with anti-cancer characteristics. Using the Scopus database, we examined literature published between 2015 and 2023, explicitly concentrating on pyrimidine derivatives as potential anti-cancer agents. Data analysis such as network analysis, co-occurrence, and visualization were conducted utilizing VOSviewer 1.6.13. Nine hundred twenty-two papers altogether, including reviews and original research, discussing the anti-cancer activity of pyrimidine compounds were identified within the specified timeframe up to January 10, 2023. Among these, 922 journal articles were selected for further analysis. Results show that Egypt led in research productivity with 267 articles (28.96%), followed by India with 234 articles (25.38%), and China with 163 articles (17.68%). Cairo University in Egypt ranked first in institutional productivity with 9 articles (0.98%), while the journal Bioorganic Chemistry was the most prolific, publishing 62 articles (6.72%) on pyrimidine compounds with anti-cancer activity. The notable increase in publications on the anti-cancer activity of pyrimidine compounds in recent years underscores the significant interest they have garnered from both pharmaceutical and academic researchers. The data presented in this study will serve as a foundational reference for future comparative studies in this area.

Cancer And Stroke - An Irish Centre’s Experience Of Emerging Trends Of Co-Diagnosis

Abstract Background Cancer is an increasingly recognised independent risk factor for the development of stroke, with emerging evidence of stroke, in the context of malignancy being its own pathophysiological subtype (Sonbol et al., 2023). Both cancer and stroke risk are associated with increasing age, with stroke mortality in cancer patients significantly higher (Sanossian et al., 2012). Due to the increasingly ageing population in Ireland, the number of those presenting with dual diagnosis is set to increase. We sought to review numbers presenting with stroke and cancer to our stroke service. Methods Patients admitted with confirmed stroke diagnosis were identified through Hospital Inpatient Enquiry (HIPE) data from March 2023 to May 2024. This cohort was then screened for a co-existing oncological diagnosis. The following variables were collected: recency of cancer diagnosis, subtype of stroke, anti-cancer therapy treatment to date, risk factors for developing cardiovascular disease using atherosclerosis cardiovascular disease score (ASCVD) and baseline CRP on admission. Results 71/320 (22%) patients admitted to our service in the defined period were identified as having a co-diagnosis of stroke and cancer (new or historical). Of those 71 patents, 8(11%) had a new or recent (<1 year) cancer diagnosis at stroke presentation and 63 were found to have a historical diagnosis (>1year). Prostate cancer represented the largest proportion of patients followed by lung and skin. 11(15%) were actively on cancer treatment at time of presentation of stroke. For patients actively on treatment, 5/11 had received platinum-based therapies. Average ASCVD risk factor score was 29.7%. Conclusion One in five patients with acute stroke had new or historical diagnosis of cancer in our cohort. A national prospective registry of patients with cancer and stroke could be useful in understanding patterns of stroke in cancer and help plan services and treatments for this specific population.

Implementing a Pilot Geriatric Oncology Service at a National Cancer Centre in Dublin

Abstract Background The American Society of Clinical Oncology and International Society of Geriatric Oncology recommend comprehensive geriatric assessment (CGA) for older adults commencing systemic anti-cancer treatments (SACTs) (1, 2). Routine CGA is lacking in cancer centres nationally. Methods A pilot, interdisciplinary geriatric-oncology (GO) clinic comprising a geriatric medicine consultant and specialist registrar, medical oncology fellow, physiotherapist and occupational therapist was established Dec 2023. New oncology patient referrals were screened applying the G8 tool; a score of ≤14 triggering referral. Polypharmacy was defined as ≥5 regular medications. Frailty was assessed using Clinical Frailty Scale (CFS) and cognition using Montreal Cognitive Assessment (MoCA). Results To date, 30 patients have attended the clinic; mean age 77.2 (SD5) years (range 68-85); 73% female, 50% with a CFS score of ≥4. Sixty-percent (n=18) were due to commence chemotherapy, the remainder hormonal or targeted treatment. Polypharmacy was identified in 66.6% (n=20), with 13.3% (n=4) having an anti-cholinergic burden score of ≥3, MoCAs were completed in 60% (n=18), of whom 77.8% (n=14) had an abnormal result (<26/30 MoCA or <18/22 MoCA blind). Twenty-six percent (n=8) reported ≥1 fall in the preceding six-months. Deprescribing interventions were completed in 40% (n=12); 58.3% (n=7) had ≥2 medications stopped. Medications most commonly deprescribed included opioids (n=2), antihypertensives (n=2), statins (n=2). Ambulatory blood pressure monitors were arranged for 33.3% (n=10) and DEXAs for 40% (n=12) and appropriately actioned. Follow up was arranged in the Falls and Syncope Unit for 7%, day hospital 10%, geriatric outpatients 10%, group psycho-oncology sessions 20%, specialist cancer rehabilitation physiotherapy service 17%. Parkinsons disease and dementia were diagnosed in 1 and 1 patients, respectively. Each patient had a detailed assessment and plan forwarded to their treating oncologist. Conclusion The development of a dedicated GO service is in line with international standards. By undergoing CGA, geriatric syndromes amenable to intervention were identified in patients.

Synthesis of Urchin-Like Au@TiO2 Nano-Carriers as a Drug-Loading System Toward Cancer Treatment.

In recent years, improving the pharmaceutical properties of drug delivery for anti-cancer treatment has become increasingly important. This is necessary to address challenges related to absorption, distribution, and stability. One potential approach solution is to attach the drug to a carrier system, such as functional noble nanomaterials, in order to improve the control of drug release and stability. Core-satellite nanoparticles (CSN) with an anisotropic morphology have enormous potential for targeted drug delivery and cancer treatment because of their large surface area, exceptional stability, and biocompatibility. We used a simple seed-mediated approach to synthesize urchin-like gold nanoparticles (ULGNPs) with a high aspect ratio and a dense network of 49 nm-sized branches, using seed solution, silver nitrate, and ascorbic acid. The ULGNPs were synthesized without a surfactant and then encapsulated with thin layers of amorphous TiO2 (ULGNPs@TiO2), resulting in an average overall size of 136±15 nm with a 27.5 nm TiO2 layer. Doxorubicin (Dox) was chosen as a model drug to assess the distribution carrier ability of ULGNPs@TiO2 core-satellite nanoparticles. The results showed 86.5 % Dox loading and 72.3 % release capacity at pH 5. The anti-cancer ability of ULGNPs@TiO2-Dox was meticulously assessed using breast cancer MCF-7 cells in the WST-1 assay. The results revealed that ULGNPs@TiO2-Dox exhibited approximately 92 % toxicity in MCF-7 cells compared to the free Dox of 89.6 % at low concentrations (5 ppm). Based on the simulation results for loading ULGNPs@TiO2 with Dox, it was observed that a structure containing five layers of Au (111) with three fixed bottom layers and two relaxed top layers, in addition to six TiO2 (100) layers, was analyzed using Grimme's DFT-D3 dispersion corrections (Scheme 1). The density functional theory (DFT) adsorption energy (Eads) shows that the amorphous TiO2 increases the Dox loading activity of ULGNPs, with Eads=-3.85 eV, negatively higher than isolated ULGNPs (Eads=-2.87 eV) and TiO2 alone (Eads=-3.61 eV). This drug carrier design has the potential to revolutionize anti-cancer treatment.

Effects of Hyperbaric Oxygen Therapy for Malignant Bowel Obstruction Caused by Peritoneal Dissemination.

This study aimed to investigate the efficacy of hyperbaric oxygen therapy (HBOT) in patients presenting with malignant bowel obstruction (MBO) and peritoneal dissemination. We retrospectively examined whether HBOT affects prognosis following MBO with peritoneal dissemination. This study included 44 patients diagnosed with MBO secondary to peritoneal dissemination at our hospital between January 2013 and December 2022. Among these patients, 30 underwent HBOT. The treatment protocol involved daily HBOT administration, comprising 100% oxygen at 2.5 atmospheres absolute for 60 min. In a univariate analysis of HBOT and non-HBOT groups, the proportion of patients able to resume eating was significantly higher in the HBOT group. Therefore, the percentage of patients in the non-HBOT group whose MBO did not improve was significantly higher than that in the HBOT group. The percentage of patients undergoing surgery or receiving anticancer treatment did not differ significantly between the groups, whereas overall survival was significantly longer in the HBOT group. Furthermore, when examining inoperable patients, significantly more individuals in the HBOT group could resume eating, and their overall survival was significantly prolonged. HBOT may increase the spontaneous resolution rate and improve long-term prognoses of patients with MBO secondary to peritoneal dissemination.

The focus on life-prolonging anticancer treatment hampers shared decision-making in people with advanced cancer: A qualitative embedded multiple-case study.

Implementing shared decision-making in oncology practice is often limited, particularly integrating the patient's context into decision-making. To improve this, we conducted a quality improvement project, CONtext. CONtext attempts to accomplish this by: (1) Integrating the patient's context into shared decision-making during consultation with the medical oncologist; (2) Actively involving the GP and case manager (a specialized oncology nurse), who often have knowledge about the patient's context, and; (3) Giving the person with advanced cancer a time-out period of up to 2 weeks to consider and discuss treatment options with others, including close family and friends. To explore how persons with advanced cancer and their involved professionals experienced shared decision-making after the introduction of CONtext. A qualitative embedded multiple-case study using in-depth interviews analysed with inductive content analysis. A purposive sample of 14 cases, each case consisting of a patient with advanced cancer and ideally their medical oncologist, case manager, and GP. Four themes were identified: shared decision-making is a dynamic and continuous process (1), in which the medical oncologist's treatment recommendation is central (2), fuelled by the patients' experience of not having a choice (3), and integrating the patient's context into shared decision-making was considered important but hampered (4), for example, by the association with the terminal phase. The prevailing tendency among medical oncologists and persons with advanced cancer to prioritize life-prolonging anticancer treatments restricts the potential for shared decision-making. This undermines integrating individual context into decision-making, a critical aspect of the palliative care continuum.

Should Patients Be Allowed to Pay Out of Pocket? The Ethical Dilemma of Access to Expensive Anti-cancer Treatments in Universal Healthcare Systems: A Dutch Case Study.

With the increasing prices of newly approved anti-cancer treatments contributing to rising healthcare costs, healthcare systems are facing complex economic and ethical dilemmas. Especially in countries with universal access and mandatory health insurance, including many European countries, the organizing of funding or reimbursement of expensive new treatments can be challenging. When expensive anti-cancer treatments are deemed safe and effective, but are not (yet) reimbursed, ethical dilemmas arise. In countries with universal healthcare systems, such as the Netherlands, this gives rise to a rather new ethical dilemma: should patients be allowed to pay out of pocket, using private funds, for medical treatments? On the one hand, to allow patients to pay for treatments out of pocket would be in line with the medical-ethical principles of beneficence and autonomy. On the other hand, allowing patients to pay out of pocket for anti-cancer treatments may lead to unequal access to medical treatments and could be considered unfair to patients who are less well-off. Thus, it could undermine the values of equality and solidarity, on which the Dutch healthcare system is built. Furthermore, out-of-pocket payments could potentially lead to financial hardship and distress for patients, which would conflict with the principle of non-maleficence. Does this mean that patients can rightfully be denied access to approved but not (yet) reimbursed anti-cancer treatments? In this article, we will use the Dutch healthcare system, which is based on equal access and solidarity, as a case study to draw attention to this-currently relatively unknown and unresolved-dilemma and to clarify the values at stake. This article contributes to current discussions about the societal problem of rising healthcare costs by informing policymakers, healthcare professionals, and ethicists about the ethical dilemma of out-of-pocket payments in universal healthcare systems, and aims to support health authorities, policymakers and health professionals in developing policy for whether to allow out-of-pocket payment-based access to newly approved but (too) expensive anti-cancer treatments.

HER3 is widely expressed across diverse subtypes of NSCLC in a retrospective analysis of archived tissue samples.

Aim: This noninterventional study (NCT05769764) aimed to characterize human epidermal growth factor receptor 3 (HER3) expression in non-small cell lung cancer (NSCLC) by patient, clinical or tumor characteristics.Methods: HER3 immunohistochemistry was performed in archival tissue samples from patients with advanced or metastatic NSCLC. Samples were scored for membrane percent positivity and intensity. Membrane H-scores were calculated.Results: Of 203 evaluable samples, HER3 expression was observed in 98.5%, including all histologies, genomic subtypes and regardless of prior systemic anticancer treatments. The median H-score was 140, and 70.4% had a HER3 intensity of 3+.Conclusion: HER3 is widely expressed in NSCLC, indicating that HER3-directed therapy may be broadly applicable across diverse subtypes of NSCLC.

Muscarinic receptor drug trihexyphenidyl can alter growth of mesenchymal glioblastoma in vivo.

Glioblastoma (GBM) is the most commonly occurring and most aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established the mesenchymal lineage of GBM (MES-GBM) as cancers with particular aggressive behavior and high levels of therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation and survival of GBM stem cells from the classical transcriptomic subtype. In a series of in vitro experiments, this study confirms the therapeutic potential of THP, by effectively suppressing the growth, proliferation and survival of MES-GBM cells with limited effects on non-tumor cells. Transcriptomic profiling of treated cancer cells identified genes and associated metabolic signaling pathways as possible underlying molecular mechanisms responsible for THP-induced effects. In vivo trials of THP in immunocompromised mice carry orthotopic MES-GBMs showed moderate response to the drug. This study further highlights the potential of THP repurposing as an anti-cancer treatment regimen but mode of action and d optimal treatment procedures for in vivo regimens need to be investigated further.

A novel HER2-specific sensor based on DARPin_9–29 and albumin binding domain for real-time fluorescence-guided tumor detection in animal model of cancer

In animal models of cancer, targeted fluorescence bioimaging, performed non-invasively and in real time, is indispensable tool for assessing tumor location, spread of metastasis, and the therapeutic potential of anticancer drugs under development.To overcome the limitation of antibodies in bioimaging applications, small artificial scaffold proteins based on ankyrin repeats (DARPins, designed ankyrin repeat proteins) are used as tumor-associated antigen binders. In this study for the first time, we assessed the potential of DARPin_9–29, the human epidermal growth factor receptor 2 (HER2) subdomain I-specific protein, genetically fused with albumin binding domain (ABD) and conjugated with Cyanine5.5 as a NIR sensor for fluorescence bioimaging of HER2-positive cancer in animal model.In vivo biodistribution studies have revealed sufficient tumor-to-background ratios at 48 h (3.17 ± 0.55) and 72 h (3.49 ± 0.64) postinjection, providing excellent contrast between the primary tumor and tissue background and allowing clear breast tumor detection. Ex vivo biodistribution has shown that ABD module in DARP-ABD sensor prevents renal reabsorption and increases tumor accumulation in more than 10-folds compared to excreting organs.To verify if DARP-ABD-Cy5.5 can demarcate HER2-positive tumor in vivo, HER2-positive syngeneic breast cancer cell line with constitutive gene expression of luciferase eFFLuc, was created. The powerful combination of bioluminescence and fluorescence imaging let to track the fluorescent anti-HER2 DARP-ABD sensor in bioluminescent HER2-positive breast tumors.Our results validate DARP-ABD as a promising sensor for fluorescence-guided imaging of HER2-positive solid cancer, which can be used in the development of improved anticancer treatment strategies.

The Effects of Pediatric Acute Lymphoblastic Leukemia Treatment on Cardiac Repolarization.

Background: In recent years, cardiac dysfunction in childhood cancer survivors has become an important issue. Studies are focusing on identifying means for the early identification of patients at risk. Considering this, our study aims to investigate 24-hour Holter electrocardiogram (ECG) repolarization changes throughout doxorubicin (DOX) and cyclophosphamide (CPM) administration in pediatric patients treated for acute lymphoblastic leukemia (ALL). Methods: This was an investigator-driven, single-center, prospective, observational study. Enrolled children had a baseline bedside ECG examination performed before starting chemotherapy (T0). Serial Holter ECG examinations were conducted at three moments during their treatment protocol: day 8 (T1), day 29 (T2), and day 36 (T3). This study evaluated several ECG repolarization parameters, such as the QT interval, corrected QT interval (QTc), and QTc dispersion, as well as ST segment variations. Results: We evaluated 37 children diagnosed with ALL. The T0 examination revealed that over a third of patients had a resting heart rate (HR) outside the normal range for their age and sex. During chemotherapy, statistically significant increases in both HR as well as QT and QTc dispersion values were noticed, especially during the first DOX administration. What is more, a significant increase in the percentage of patients with ST segment depression from T1 to T2 and T3 was noticed. Rhythm disturbances were rare in the study population, with only a few patients presenting ventricular or supraventricular extrasystoles. Conclusions: This study reveals silent repolarization changes occurring early during anticancer treatment in children treated for ALL. These findings could aid in a better understanding of the cardiac toxicity mechanism, and they could potentially improve cardiac risk stratification for oncologic patients. Because of the small number of patients, our results need to be validated by larger studies.

Nanomedicine Advancements in Cancer Therapy: A Scientific Review

Cancer nanomedicines, characterized by submicrometer-sized formulations, aim to optimize the biodistribution of anticancer drugs by minimizing off-target effects, reducing toxicity, enhancing target site accumulation, and improving overall efficacy. Numerous nanomedicines have been developed to improve the effectiveness and safety of traditional anticancer treatments. These include formulations with carbon nanotubes, nanodiamonds, enzyme-responsive nanoparticles for controlled drug release, dendrimers as nanoparticle drug carriers, quantum dot nanocarrier systems for precise drug delivery, solid lipid nanoparticles, and polymeric nanoparticles designed for targeted drug delivery. Additionally, nanotechnology has been explored in cancer treatment through gene therapy. Despite these advances, the complex nature of carrier materials and functional integration presents challenges in preparing these candidates for clinical translation. Nanotechnology, with its unique features at the nanoscale, offers novel possibilities for developing cancer therapies while increasing efficacy and safety. Although only a few nanotherapeutics have obtained clinical approval, exciting uses for nanotechnology are on the horizon. Nanoparticles possess unique transport, biological, optical, magnetic, electrical, and thermal capabilities due to their small size within the light wavelength spectrum. This results in high surface area-to-volume ratios, allowing for the incorporation of various supporting components in addition to active medicinal substances. These properties aid in solubilization, degradation protection, delayed release, immune response evasion, tissue penetration, imaging, targeted distribution, and triggered activation. In summary, the future of nanomedicine holds promise for introducing innovative platforms in cancer treatment. The research presented underscores the potential for nanoparticles to revolutionize anticancer therapies, enhancing the overall therapeutic approach.

Benzimidazole-based small molecules as anticancer agents targeting telomeric G-quadruplex and inhibiting telomerase enzyme.

Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.

Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium

Aging epithelia are colonized by somatic mutations, which are subjected to selection influenced by intrinsic and extrinsic factors. The lack of suitable culture systems has slowed the study of this and other long-term biological processes. Here, we describe epithelioids, a facile, cost-effective method of culturing multiple mouse and human epithelia. Esophageal epithelioids self-maintain without passaging for at least 1 year, maintaining a three-dimensional structure with proliferative basal cells that differentiate into suprabasal cells, which eventually shed and retain genomic stability. Live imaging over 5 months showed that epithelioids replicate in vivo cell dynamics. Epithelioids support genetic manipulation and enable the study of mutant cell competition and selection in three-dimensional epithelia, and show how anti-cancer treatments modulate competition between transformed and wild-type cells. Finally, a targeted CRISPR–Cas9 screen shows that epithelioids recapitulate mutant gene selection in aging human esophagus and identifies additional drivers of clonal expansion, resolving the genetic networks underpinning competitive fitness.

Current understanding of modulated electro-hyperthermia in cancer treatment

Traditional hyperthermia involves increasing the temperature at the tumor site to above 39 ℃, inducing death in cancer cells. Although hyperthermia is an effective cancer treatment, its clinical application has decreased due to potential complications, including damage to surrounding normal tissue. In recent years, modulated electro-hyperthermia (mEHT) has emerged as an effective and safe treatment modality. mEHT selectively heats tumor cells to 42–43 °C, while reducing the average temperature in the treatment area, including the surrounding normal tissue, compared to conventional methods. Additionally, mEHT may be used in combination with systemic chemotherapy and radiation therapy in tumor treatment, providing a synergistic effect to increase efficacy. As chemotherapy and radiation therapy technologies advance, the application of combined mEHT may improve clinical outcomes. In this study, we review and discuss reports on the clinical outcomes of mEHT combined with chemotherapy and/or radiation therapy, which are established anticancer treatments.

Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.

Certain anticancer therapies inevitably increase the risk of cardiovascular events, now the second leading cause of death among cancer patients. This underscores the critical need for developing effective drugs or regimens for cardiovascular protection. Statins possess properties such as antioxidative stress, anti-inflammatory effects, antifibrotic activity, endothelial protection, and immune modulation. These pathological processes are central to the cardiotoxicity associated with anticancer treatment. There is prospective clinical evidence confirming the protective role of statins in chemotherapy-induced cardiotoxicity. Numerous preclinical studies have demonstrated that statins can ameliorate heart and endothelial damage caused by radiotherapy, although clinical studies are scarce. In the animal models of trastuzumab-induced cardiomyopathy, statins provide protection through anti-inflammatory, antioxidant, and antifibrotic mechanisms. In animal and cell models, statins can mitigate inflammation, endothelial damage, and cardiac injury induced by immune checkpoint inhibitors. Chimeric antigen receptor (CAR)-T cell therapy-induced cardiotoxicity and immune effector cell-associated neurotoxicity syndrome are associated with uncontrolled inflammation and immune activation. Due to their anti-inflammatory and immunomodulatory effects, statins have been used to manage CAR-T cell therapy-induced immune effector cell-associated neurotoxicity syndrome in a clinical trial. However, direct evidence proving that statins can mitigate CAR-T cell therapy-induced cardiotoxicity is still lacking. This review summarizes the possible mechanisms of anticancer therapy-induced cardiotoxicity and the potential mechanisms by which statins may reduce related cardiac damage. We also discuss the current status of research on the protective effect of statins in anticancer treatment-related cardiovascular disease and provide directions for future research. Additionally, we propose further studies on using statins for the prevention of cardiovascular disease in anticancer treatment.