Histotripsy: A Promising Modality for Cancer Treatment

Conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, have significantly advanced cancer treatment. However, these modalities often face limitations such as systemic toxicity, lack of specificity, and the emergence of resistance. Recent advancements in genetic engineering and synthetic biology have rekindled interest in using bacteria as a novel therapeutic approach in oncology. This comprehensive review explores the potential of microbial therapeutics, particularly bacterial therapies, in the treatment of cancer. Bacterial therapies offer several unique advantages, such as the ability to selectively target and colonize hypoxic and necrotic regions of tumors, areas typically resistant to conventional treatments. The review delves into the mechanisms through which bacteria exert antitumor effects, including direct tumor cell lysis, modulation of the immune response, and delivery of therapeutic agents like cytotoxins and enzymes. Various bacterial species, such as Salmonella, Clostridium, Lactobacillus, and Listeria, have shown promise in preclinical and clinical studies, demonstrating diverse mechanisms of action and therapeutic potential. Moreover, the review discusses the challenges associated with bacterial therapies, such as safety concerns, immune evasion, and the need for precise targeting, and how recent advances in genetic engineering are being used to overcome these hurdles. Current clinical trials and combination strategies with conventional therapies are also highlighted to provide a comprehensive overview of the ongoing developments in this field. In conclusion, while bacterial therapeutics present a novel and promising avenue in cancer treatment, further research and clinical validation is required to fully realize their potential. This review aims to inspire further exploration into microbial oncology, paving the way for innovative and more effective cancer therapies.

The targeting of vascular endothelial growth factor A (VEGFA), a crucial regulator of both normal and pathological angiogenesis, has revealed innovative therapeutic approaches in oncology and ophthalmology. The first VEGFA inhibitor, bevacizumab, was approved by the US Food and Drug Administration in 2004 for the first-line treatment of metastatic colorectal cancer, and the first VEGFA inhibitors in ophthalmology, pegaptanib and ranibizumab, were approved in 2004 and 2006, respectively. To mark this tenth anniversary of anti-VEGFA therapy, we discuss the discovery of VEGFA, the successes and challenges in the development of VEGFA inhibitors and the impact of these agents on the treatment of cancers and ophthalmic diseases.

12086 Background: New treatments and early detection measures have led to declines in cancer mortality rates and a growing population of cancer survivors at risk of short- and long-term effects of cancer and cancer treatment (C&CT), including cardiovascular disease (CVD). Although shared risk factors may contribute, several C&CT-related mechanisms including inflammation, treatment-related cardiotoxicity, and coagulation disorders may play a role. There are several studies exploring the link between C&CT and CVD; however, many do not examine risk stratified by cancer type or disease extent, nor investigate the impact of different treatment modalities. Methods: This analysis utilized data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, an international, multi-center, double-blinded randomized controlled trial that investigated the benefits and risks of aspirin in healthy older people. Multivariate time-dependent Cox regression models (adjusted for clinically significant factors including age, gender, smoking, and metabolic disease) were used to investigate the impact of C&CT on myocardial infarction, stroke, hospitalization for heart failure, and a composite endpoint combining these. Crude incidence rates were estimated using a competing risks regression model. Subgroup analysis was performed by metastatic status, cancer type, and treatment modality. Results: Of the 19,114 ASPREE participants (56% female; median age 75.1 years; median follow up 4.7 years), 1,933 received a post-randomisation cancer diagnosis. Participants with cancer had a greater rate and risk of CVD than those without cancer (15.3 per 1000 person-years (/1000pyrs] vs 10.5/1000pyrs, respectively; Hazard Ratio [HR] = 1.70, 95% Confidence Interval [CI] 1.32-2.10). The greatest increase in risk was seen for hospitalization for heart failure (HR 2.00, 1.18-3.38, 95% CI 1.18-3.38), although increases in risk were also seen for myocardial infarction, all-stroke, and ischaemic stroke. In subgroup analysis by cancer type, blood cancer (HR 2.33, 95% CI 1.25-4.36), lung cancer (HR 2.76, 95% CI 1.23-6.19), and melanoma (HR 1.97, 95% CI 1.02-3.82) were associated with an increased risk of composite CVD. ‘Any cancer treatment’ conferred increased risk of hospitalisation for heart failure (HR 1.78, 95% CI 1.15-2.75), although individual treatment modalities, including cytotoxic chemotherapy, targeted therapy, and radiotherapy conferred increased risks of various cardiovascular outcomes. Conclusions: Our findings indicate that both cancer and anti-cancer treatment confer risk for CVD in the elderly, the magnitude of which varied depending on cancer type and treatment modality. Given the implications of cardiovascular events for quality of life and mortality, these results support the integration of CVD screening and management into routine care for cancer survivors.

Anxiety in patients with breast cancer undergoing treatment: A systematic review

Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt's seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD.

The efficacy of directly killing tumors by conventional cancer therapies, such as chemotherapy and radiotherapy, has been for several decades well established. But, a suppressed immune response might become a lethal side effect after repeated cycles of intensive treatment. Recently, achievements in immune checkpoint inhibitors and adoptive T cell-mediated immunotherapies have resulted in changes in frontline management of advanced cancer diseases. However, accumulated evidence indicates that immunotherapeutic and conventional strategies alone are often ineffective to eradicate big tumors or metastasis. To improve the outcomes of treatment for advanced cancer diseases, the combination of conventional cancer treatment with various immunotherapeutic approaches has been attempted and has shown potential synergistic effects. Recent studies have unexpectedly demonstrated that some strategies of conventional cancer treatment can regulate the immune response positively, thus the understanding of how to adapt conventional treatment for immunotherapy is crucial to the design of effective combination therapy of conventional treatment with immunotherapy. Here, we review both experimental and clinical studies on the therapeutic effect and its mechanisms of combining conventional therapy with immunotherapy in treatment of cancer.

Bacteria play a crucial role in human health and disease pathogenesis. In recent years, the therapeutic potential of probiotics has gained increasing attention, with studies suggesting their application in treating various diseases, including cancer. We evaluated clinical data supporting the use of oral and topical probiotics for skin malignancies by conducting a literature search in PubMed and Google Scholar. Although limited, clinical trials investigating probiotics in cancer prevention and treatment have shown promising results, particularly in controlling tumor progression and enhancing therapeutic outcomes. Emerging research suggests that probiotics may contribute to skin cancer prevention by modulating the gut and skin microbiomes, enhancing immune responses, exerting antioxidant and anti-inflammatory effects, and inducing apoptosis. Given their antiproliferative and pro-apoptotic effects on carcinoma cells, probiotic-based therapies may serve as potential cancer-preventive agents and adjunctive treatments during conventional therapies. Key findings from our review highlight the ability of probiotics to influence cancer progression through immune regulation, apoptosis induction, and modulation of inflammatory pathways. However, further well-designed clinical trials are needed to validate these findings and establish probiotics as a viable therapeutic approach in oncology.

113. Potent Therapeutic Efficacy of Neurotensin Receptor-Targeting and Extracellular Matrix-Degrading Oncolytic Adenovirus in an Orthotopic Pancreatic Tumor Model

Potent antitumor effect of neurotensin receptor-targeted oncolytic adenovirus co-expressing decorin and Wnt antagonist in an orthotopic pancreatic tumor model

Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment. In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack. We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment.

Tumor, as the second leading cause of death globally, following closely behind cardiovascular diseases, remains a significant health challenge worldwide. Despite the existence of various cancer treatment methods, their efficacy is still suboptimal, necessitating the development of safer and more efficient treatment strategies. Additionally, the advancement of personalized therapy offers further possibilities in cancer treatment. Nanomedicine, as a promising interdisciplinary field, has shown tremendous potential and prospects in the diagnosis and treatment of cancer. As an emerging approach in oncology, the application of nanomedicine in personalized cancer therapy primarily focuses on targeted drug delivery systems such as passive targeting drug delivery, active targeting drug delivery, and environmentally responsive targeting drug delivery, as well as imaging diagnostics such as tumor biomarker detection, tumor cell detection, and in vivo imaging. However, it still faces challenges regarding safety, biocompatibility, and other issues. This review aims to explore the advances in the use of nanomaterials in the field of personalized cancer diagnosis and treatment and to investigate the prospects and challenges of developing personalized therapies in cancer care, providing direction for the clinical translation and application.

Photodynamic therapy (PDT) is considered to be a minimally invasive treatment modality which shows great promise in premalignant and malignant conditions of the head and neck. This therapy can be applied before or after any of the conventional treatment modalities (ie surgery, radiotherapy or chemotherapy) and the treatment can be repeated as much as is needed at the same site. PDT uses photosensitizing drugs that are activated by exposure to light of a specific wavelength. Illumination of the suspected premalignant or malignant site by light at the activating wavelength results in cellular destruction by a non-free radical oxidative process. Most photosensitizers are administered systemically, although some can be applied topically in the treatment of skin cancer. Recent developments in photosensitizers and light delivery systems have substantially reduced treatment times and residual photosensitivity, while increasing the achievable depth of necrosis. Compared with standard approaches, PDT can achieve equivalent or greater efficacy in the treatment of premalignant and malignant lesions in the head and neck, with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients. It can be repeated to debulk large tumours progressively, and it can also be applied through interstitial light delivery to large solid tumours. Photodynamic therapy is now shown to achieve equivalent or greater efficacy than standard treatment of premalignant and malignant lesions in the head and neck, with greatly reduced morbidity and disfigurement.

Tumor-Treating Fields: A fourth modality in cancer treatment, new practice updates.

FLASH radiotherapy (FLASH RT) is an innovative modality in cancer treatment that delivers ultrahigh dose rates (UHDRs), distinguishing it from conventional radiotherapy (CRT). FLASH RT has demonstrated the potential to enhance the therapeutic window by reducing radiation-induced damage to normal tissues while maintaining tumor control, a phenomenon termed the FLASH effect. Despite promising outcomes, the precise mechanisms underlying the FLASH effect remain elusive and are a focal point of current research. This review explores the metabolic and cellular responses to FLASH RT compared to CRT, with particular focus on the differential impacts on normal and tumor tissues. Key findings suggest that FLASH RT may mitigate damage in healthy tissues via altered reactive oxygen species (ROS) dynamics, which attenuate downstream oxidative damage. Studies indicate the FLASH RT influences iron metabolism and lipid peroxidation pathways differently than CRT. Additionally, various studies indicate that FLASH RT promotes the preservation of mitochondrial integrity and function, which helps maintain apoptotic pathways in normal tissues, attenuating damage. Current knowledge of the metabolic influences following FLASH RT highlights its potential to minimize toxicity in normal tissues, while also emphasizing the need for further studies in biologically relevant, complex systems to better understand its clinical potential. By targeting distinct metabolic pathways, FLASH RT could represent a transformative advance in RT, ultimately improving the therapeutic window for cancer treatment.

BackgroundChemotherapy and radiation reduce tumor burden by killing tumor cells, but as a consequence, create tumor cell debris. The debris of dead cancer cells acts as a source of tumor‐stimulation, via inflammation, on the few surviving cells contributing to tumor relapse. Thus chemotherapy may be a doubled‐edged sword. Maresin 1 (MaR1), a key mediator of inflammation resolution, is biosynthesized by human macrophages from endogenous docosahexaenoic acid. We hypothesize that maresins represent a novel modality in cancer treatment by inhibiting tumor growth and metastasis by enhancing endogenous clearance of tumor debris by macrophage phagocytosis.ResultsFlow cytometry confirmed chemotherapy and targeted therapy (tamoxifen)‐induced apoptotic tumor cell debris. MaR1 stimulated macrophage phagocytosis of chemotherapy‐induced cell debris (e.g. breast carcinoma and melanoma) by 123% to 206%. Systemic administration of MaR1 inhibits primary tumor growth by promoting the resolution of inflammation without toxicity. ConclusionsWe demonstrate for the first time that maresins inhibit primary tumor growth and metastasis via the stimulation of macrophage phagocytosis of chemotherapy‐induced tumor cell debris. Thus, the MaR1 pathway or the enhancement of endogenous resolution processes, offers an entirely novel approach for clearing tumor cells debris induced by conventional cancer therapy.