Emerging Treatment Strategies Research Articles

Advancements in the Treatment of Diabetic Macular Edema: Current Strategies and Future Directions

This narrative review examines current and emerging treatment strategies for diabetic macular edema (DME), a complication of diabetic retinopathy characterised by fluid accumulation in the macula, which can lead to vision impairment. The incidence of DME is particularly high in patients with long-standing diabetes and advanced retinopathy. The current treatment options for DME include anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser therapies. Anti-VEGF agents, including bevacizumab, ranibizumab, aflibercept, and the more recently developed brolucizumab and faricimab, have been demonstrated to reduce macular thickness and improve visual acuity. Brolucizumab offers the advantage of fewer injections due to its longer duration of action, although it carries a higher risk of ocular inflammation compared to other anti-VEGF agents. The dual inhibition of the VEGF and angiopoietin-2 (Ang-2) pathways by faricimab may enhance vascular stability and reduce inflammation, potentially improving patient outcomes. Steroid therapies, including dexamethasone, fluocinolone acetonide, and triamcinolone acetonide, represent an alternative for patients who do not respond adequately to anti-VEGF treatment. Laser therapies, including focal, navigated, and subthreshold laser treatments, remain a crucial component in the management of DME, with the ability to seal leaking vessels and reduce fluid accumulation. In order to achieve the best outcomes for patients, it is essential to continue to advance these treatment modalities and adopt a personalised, multifaceted approach.

Breaking the Mold: Trailblazing Melanoma Therapy Beyond Checkpoint Through Innovative Approaches.

Melanoma has long been a difficult malignancy to treat with low response rates to standard chemotherapies. In recent years, the use of immune checkpoint inhibitors have demonstrated promising results, paving the way for the use of the rapidly developing novel immune targeting therapies. In this review, we look beyond immune checkpoint inhibitor treatments and summarize several emerging treatment strategies for melanoma, including neoantigen vaccines, conventional antibody drug-conjugates, and bispecific T-cell engager therapies.

Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.

Atrial fibrillation (AF) is a continually growing health-care burden that often presents together with metabolic disorders, including diabetes mellitus and obesity. Current treatments often fall short of preventing AF and its adverse outcomes. Accumulating evidence suggests that metabolic disturbances can promote the development of AF through structural and electrophysiological remodelling, but the underlying mechanisms that predispose an individual to AF are aetiology-dependent, thus emphasizing the need for tailored therapeutic strategies to treat AF that target an individual's metabolic profile. AF itself can induce changes in glucose, lipid and ketone metabolism, mitochondrial function and myofibrillar energetics (as part of a process referred to as 'metabolic remodelling'), which can all contribute to atrial dysfunction. In this Review, we discuss our current understanding of AF in the setting of metabolic disorders, as well as changes in atrial metabolism that are relevant to the development of AF. We also describe the potential of available and emerging treatment strategies to target metabolic remodelling in the setting of AF and highlight key questions and challenges that need to be addressed to improve outcomes in these patients.

Abstract PO3-01-04: Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study

Abstract Introduction Neoadjuvant therapy (NAT) is considered the standard of care in patients with HER2-positive breast cancer mainly due to the possibility to adjust the post-neoadjuvant treatment based on the tumor response to NAT. However, there is no convincing evidence on a survival benefit with NAT compared to adjuvant therapy (AT) for HER2-positive breast cancer. The aim of the present study was to compare the two therapeutic strategies in a register-based cohort of Swedish patients with primary operable HER2-positive breast cancer. Method The research database BCBaSe 3.0, which is based on the Swedish National Quality breast cancer register, was used to identify patients with primary operable HER2-positive breast cancer that diagnosed between 2008 and 2020 and received either NAT or AT including chemotherapy and trastuzumab. To mitigate confounding by indication bias, propensity score matching (PSM) with 1:1 matching was applied. The effectiveness of the two therapeutic strategies was investigated through analyzing distant disease-free survival (DDFS), breast-cancer specific survival (BCSS), and overall survival (OS). Multivariate Cox regression analyses were performed for the outcomes of interest to provide Hazard Ratios (HR) and corresponding 95% Confidence Intervals (CI). Results In total, 7258 patients with primary operable HER2-positive breast cancer treated with either NAT or AT were identified, 1789 (24.6%) received NAT and 5469 (75.4%) AT. After 1:1 PSM, 1258 patients in each therapeutic strategy were available for comparisons. After a median follow-up of 63 months, no statistically significant differences between NAT and AT were observed in either outcome (HR for DDFS: 0.97; 95% CI: 0.72 – 1.30; HR for BCSS: 0.69; 95% CI: 0.45 – 1.07; HR for OS: 0.72; 95% CI: 0.50 – 1.05). In subgroup analyses, estrogen-receptor status did not impact the results that remained statistically non-significant between NAT and AT whereas in patients with clinically positive lymph node status, NAT resulted in better BCSS (HR: 0.44; 95% CI: 0.22 – 0.89) and OS (HR: 0.49; 95% CI: 0.29 – 0.90). The latter trend was not evident in patients with clinically negative lymph node status. Conclusion Our study results confirm the equivalence of NAT and AT in terms of prognosis for patients with operable HER2-positive disease and imply a potential benefit of NAT compared to AT in patients with clinically positive lymph node status. Considering the emerging treatment strategies in HER2-positive breast cancer patients treated with NAT (pertuzumab as a part of NAT, T-DM1 as post-neoadjuvant therapy) that have been shown to improve survival but are not reflected in the study cohort, NAT should be considered as the strategy with the higher possibility to improve long-term prognosis for patients with HER2-positive disease. Citation Format: Servah Hosseini-Mellner, Åsa Wickberg, Antonis Valachis, Andreas Karakatsanis. Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-04.

Psychosocial Support in Pulmonary Rehabilitation.

Pulmonary rehabilitation (PR) improves exercise capacity and quality of life (QOL) while reducing dyspnea in patients with COPD. However, little is known about the efficacy of PR, cognitive behavioral therapy (CBT), or antidepressant drug therapy on psychosocial factors in patients with COPD. Knowledge gaps include which therapy is most efficacious, what barriers exist for each treatment, and the optimal duration of each intervention. Potential barriers to antidepressant therapy include patient fears of potential adverse effects, apprehension and misconception, and stigma related to depression. Both CBT and PR reduce anxiety and depressive symptoms in short-term studies. However, their potential benefits over medium-to-long-term follow-up and specifically on psychosocial factors warrant exploration. Furthermore, new emerging treatment strategies such as the collaborative care model and home-based telehealth coaching are promising interventions to promote patient-centered care treatment and reduce psychosocial factors adversely affecting patients with COPD. This update and critical synthesis reviews the effectiveness of both pharmacologic and non-pharmacologic interventions on psychosocial factors in patients with COPD. It also provides brief screening tools used in the assessment of anxiety and depression for patients with COPD.

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.

Systemic sclerosis (SSc) is a heterogeneous disease characterized by autoimmunity, vasculopathy, and fibrosis which affects the skin and internal organs. One key aspect of SSc vasculopathy is pulmonary arterial hypertension (SSc-PAH) which represents a leading cause of morbidity and mortality in patients with SSc. The pathogenesis of pulmonary hypertension is complex, with multiple vascular cell types, inflammation, and intracellular signaling pathways contributing to vascular pathology and remodeling. In this review, we focus on shared molecular features of pulmonary hypertension and those which make SSc-PAH a unique entity. We highlight advances in the understanding of the clinical and translational science pertinent to this disease. We first review clinical presentations and phenotypes, pathology, and novel biomarkers, and then highlight relevant animal models, key cellular and molecular pathways in pathogenesis, and explore emerging treatment strategies in SSc-PAH.

Considering New and Emerging Treatment Strategies for Depression: Beyond STAR*D and the Monoamines

Abstract: While the number of treatment options for major depressive disorder (MDD) has grown in recent years, the lack of quality data to guide optimal modality selection has lessened the potential impact of having a more diverse set of mechanistic approaches to treatment. The last attempt to investigate treatment sequencing for MDD was the Sequenced Treatment Alternatives for Relief of Depression Study (STAR*D), which gave rise to the concept of treatment-resistant depression (TRD) as a failure to respond to two or more monoaminergic antidepressants. However, a recent reanalysis of the STAR*D data indicates that most patients do not remit even when treated with multiple traditional antidepressants. Given these new results, labeling the majority of patients as treatmentresistant is not appropriate or useful. If monoamine-based drugs are not that effective for the majority of MDD patients, then it is necessary to consider the mechanistically distinct pharmacological and non-pharmacological treatment options that have emerged recently, including brain stimulation, glutamate receptor modulators, and psychedelic medicines. While these new treatment modalities have the potential to enhance patient outcomes, clinicians and patients currently lack a framework to guide their choices other than cost, feasibility, personal preference, and certain medical contraindications. Here, we review alternative treatment modalities for monoamine non-responders and consider the possibility that there will be new first-line therapies for MDD. We will review how treatment decisions for these patients are currently being made and how developments in precision psychiatry may help guide rational treatment selection in the future.

Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer

BackgroundImmune checkpoint inhibitor (ICI) combinations represent an emerging treatment strategies in cancer. However, their efficacy in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC) is variable. Here, a...

Advances in Development of Novel Therapeutic Strategies against Multi-Drug Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) with multi-drug resistance (MDR) is a major cause of serious healthcare-associated infections, leading to high morbidity and mortality. This opportunistic pathogen is responsible for various infectious diseases, such as those seen in cystic fibrosis, ventilator-associated pneumonia, urinary tract infection, otitis externa, and burn and wound injuries. Due to its relatively large genome, P. aeruginosa has great diversity and can use various molecular mechanisms for antimicrobial resistance. For example, outer membrane permeability can contribute to antimicrobial resistance and is determined by lipopolysaccharide (LPS) and porin proteins. Recent findings on the regulatory interaction between peptidoglycan and LPS synthesis provide additional clues against pathogenic P. aeruginosa. This review focuses on recent advances in antimicrobial agents and inhibitors targeting LPS and porin proteins. In addition, we explore current and emerging treatment strategies for MDR P. aeruginosa, including phages, vaccines, nanoparticles, and their combinatorial therapies. Novel strategies and their corresponding therapeutic agents are urgently needed for combating MDR pathogens.

Gut Microbiome and Polycystic Ovary Syndrome: Interplay of Associated Microbial-Metabolite Pathways and Therapeutic Strategies.

Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.

Epigenetic dysregulation and emerging treatment strategies in myelodysplastic syndromes

The epigenome regulates transcription of target genes through DNA methylation- or histone methylation/acetylation/phosphorylation/ubiquitination-mediated alteration of genomic function or chromatin conformation. Recent genomic studies have shown that multiple genes encoding epigenetic regulators are frequently and recurrently mutated in MDS, suggesting that epigenetic dysregulation is significantly associated with the molecular pathogenesis and clinical features of MDS. In this review, we will present our recent findings together with others, focusing on physiological molecular functions of epigenetic regulators recurrently mutated in MDS and on functional correlation between dysregulated epigenomic regulators and molecular pathogenesis/clinical features of MDS.

Metastasis-directed therapy: new standard or too early to change paradigm?

SummaryMetastasis-directed therapy (MDT) is an emerging treatment strategy for patients with oligometastatic prostate cancer (PCa), particularly for oligorecurrent disease. This review aims to summarize findings from several prospective trials in the setting of oligorecurrent PCa. We found that MDT is feasible, has high tolerability, and is effective in terms of local control of treated lesions and of deferring disease progression in well-selected patients. Selecting patients for MDT requires thoughtful consideration of factors such as the castration status, the number of detected metastases, and the imaging modality used for metastasis detection. Notably, the studies included in this review varied in terms of these factors, complicating the comparability of their results. Despite the existence of several prospective clinical trials in the field, there is an absence of high-level evidence attributable to the lack of phase 3 clinical trials. As a result, current guidelines recommend the administration of MDT exclusively within the context of clinical trials. Despite this, retrospective series indicate that MDT is already frequently utilized outside of clinical trials.

Synthesis of iron-boride/carbon-nitride composites and their applications in chemodynamic therapy

Chemodynamic therapy (CDT) is an emerging treatment strategy that inhibits tumor growth by catalyzing the generation of reactive oxygen species (ROS), such as hydroxyl radicals (•OH), using specific nanomaterials. Herein, we have developed a new class of iron-based nanomaterials, i.e., iron-based borides (FeB), using the superchaotropic effect of a boron cluster (closo-[B12H12]2–) and organic ligands, followed by high-temperature calcination. Experimental data and theoretical calculations revealed that FeB nanoparticles exhibit a Fenton-like effect, efficiently decomposing hydrogen peroxide into •OH and thus increasing the concentration of ROS. FeB nanomaterials demonstrate excellent catalytic performance, efficiently generate ROS, and exert significant antitumor effects in cell experiments and animal models. Therefore, FeB nanomaterials have considerable potential for application in tumor treatment and offer new insights for the development of novel and efficient cancer therapy strategies.

Emerging treatment strategies in chronic B-cell malignancies—News from ICML 2023

SummaryImplementation of targeted drugs in the treatment landscape of indolent B‑cell malignancies has facilitated long-term remissions and reduced treatment-related toxicities for a substantial proportion of patients across several disease entities. Yet, adverse prognostic genetic aberrations such as TP53 dysfunctions and short-lived remissions after front-line therapy cannot be fully compensated with currently licensed novel agents thereby predisposing affected patients to inferior clinical outcomes in the long run. Moreover, acquired resistance and increasing drug intolerability typically evolving with continuous treatment remain challenges to overcome in daily clinical practice. With these unmet medical needs in mind, several clinical trials are currently investigating the efficacy and feasibility of time-limited novel drug combinations across several indolent B‑cell malignancies. This short review aims to give an update on novel clinical trial data presented at the International Conference of Malignant Lymphoma 2023.

Adoptive cell immunotherapy for breast cancer: harnessing the power of immune cells.

Breast cancer is the most prevalent malignant neoplasm worldwide, necessitating the development of novel therapeutic strategies owing to the limitations posed by conventional treatment modalities. Immunotherapy is an innovative approach that has demonstrated significant efficacy in modulating a patient's innate immune system to combat tumor cells. In the era of precision medicine, adoptive immunotherapy for breast cancer has garnered widespread attention as an emerging treatment strategy, primarily encompassing cellular therapies such as tumor-infiltrating lymphocyte therapy, chimeric antigen receptor T/natural killer/M cell therapy, T cell receptor gene-engineered T cell therapy, lymphokine-activated killer cell therapy, cytokine-induced killer cell therapy, natural killer cell therapy, and γδ T cell therapy, among others. This treatment paradigm is based on the principles of immune memory and antigen specificity, involving the collection, processing, and expansion of the patient's immune cells, followed by their reintroduction into the patient's body to activate the immune system and prevent tumor recurrence and metastasis. Currently, multiple clinical trials are assessing the feasibility, effectiveness, and safety of adoptive immunotherapy in breast cancer. However, this therapeutic approach faces challenges associated with tumor heterogeneity, immune evasion, and treatment safety. This review comprehensively summarizes the latest advancements in adoptive immunotherapy for breast cancer and discusses future research directions and prospects, offering valuable guidance and insights into breast cancer immunotherapy.

Biomarkers and Treatment Strategies for Breast Cancer Recurrence.

Despite recent treatment advancements, breast cancer remains a life-threatening disease. Although treatment is successful in the early stages, a significant proportion of individuals with breast cancer eventually experience a recurrence of the disease. Breast tumour recurrence poses a significant medical issue. Despite tumours being a primary cause of mortality, there remains a limited understanding of the fundamental mechanisms underlying tumour recurrence. The majority of the time, after surgery or medical treatment, this metastatic disease manifests itself after the disease is undiagnosed for a considerable amount of time. This phenomenon is commonly referred to as a relapse or recurrence. Metastatic breast cancer has the potential to recur at varying intervals, ranging from a few months to several decades following the initial diagnosis and treatment. This article aimed to summarise the primary causes of breast cancer recurrence and highlight the key issues that need to be addressed in order to effectively decrease the mortality rate among breast cancer patients. This article discusses various therapeutic approaches currently employed and emerging treatment strategies that hold the potential for the complete cure of cancer.

Intraoperative radiotherapy after resection of brain metastases located in the posterior fossa. Analysis of postoperative morbidity and mortality in a single center cohort

IntroductionIn order to improve surgical outcome and accelerate the adjuvant oncologic therapy, intraoperative Radiotherapy (IORT) has become a treatment option in oncologic surgery for various diseases including glioma and brain metastasis (BM). BMs are often located in the cranial posterior fossa (PF) requiring specific surgical considerations due to its complex anatomy. Up until now, data on IORT for BMs is limited and detailed description in the use of IORT for lesions in the PF is lacking. Our aim is to provide more insight into this emerging treatment strategy. MethodsWe performed a retrospective analysis of patients receiving surgery for BMs and undergoing IORT at our institution. Each patient was discussed at the interdisciplinary tumor board decision before the intervention. Patient characteristics, functional status (Karnofsky Performance Score, KPS) before and after surgery, disease (recursive partitioning analysis, lesion size) and operative parameters were analyzed. Adverse events (AE) were recorded up until 30 days after the intervention and rated according to the Clavien Dindo Rating scale. ResultsNine patients (5 female) were included. None underwent prior radiotherapy (RT). Mean age was 66 ± 11 years. Preoperative median KPS was 80%. Mean BM diameter was 3.2 ± 0.9 cm. There was no statistically significant deterioration of the functional status after the intervention. Two patients experienced AEs with both of them needing revision surgery. ConclusionSurgery for BMs with IORT in the PF seems safe and feasible. Further studies are needed to evaluate the influence of IORT on long-term outcome after BM surgery.

Creation and Implementation of an Interdisciplinary Workflow for CBCT-Based Online Adaptive Radiotherapy

CBCT-based online adaptive radiotherapy (OART) is an emerging treatment strategy to replan based on the anatomy of the day while the patient remains on the couch. OART is not just an add-on to the current workflow; it necessitates a new approach across the patient's path of care, from CT simulation to treatment delivery. OART requires the addition of duties to clinical personnel, strategies to create auto-plan templates, and monitoring the "black box" adaptation process. Studies have shown that OART implementation is limited by its resource-intensive nature and the risks associated with the treatment approach. We hypothesized that the implementation of an interdisciplinary, streamlined workflow and checklists would enhance the OART treatment efficiency, prevent medical errors from the adaptation, and minimize the burden on clinicians. An interdisciplinary OART working group comprising radiation oncologists, medical physicists, dosimetrists, and therapists was created to enable weekly knowledge sharing, workflow design, implementation, and continuous process improvement. 213 adaptive sessions from 5 treatment sites (pancreas, bladder, prostate, rectum, anus) were treated on a CBCT-based OART platform in a single institutional study. An evaluation of the treatment safety and workflow time was performed for each adaptive session. The OART workflow was divided into four sub-workflows: 1) pre-treatment site-specific template preparation, 2) pre-treatment initial planning and verification, 3) on-treatment procedure, and 4) post-treatment evaluation. The sub-processes involved 4, 8, 13, and 4 separate, sequentially tasks, respectively, and a total of 11 task checklists. The template preparation is a new process developed for site-specific, standardized physician template directives, automated planning template development, and testing for its accuracy and robustness. The planning templates generated high-quality initial plans automatically within minutes once structures were segmented on the planning CT. This process was replicated during treatment using the CBCT. The median (interquartile range) online procedure time, defined as the time from initial CBCT to plan approval, of the five treatment sites (pancreas, bladder, prostate, rectum, anus) was 22.1 (19.2-24.8) min, 16.5 (15.3-17.5) min, 14.7 (13.9-17.4) min, 17 (15.3-19.7) min, and 24 (21.4-25.8) min, respectively. Safety assessment determined that no treatment deviations were observed. Creating an interdisciplinary, standardized workflow and checklists allowed the safe delivery of OART with clinically feasible online procedure time and significantly reduced initial planning time compared with traditional EBRT. The unique workflow is essential to minimize the burden on the care team, increase patient safety, and access to OART.

Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy

Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.

Advances in immunotherapy for osteosarcoma: a review of emerging treatment strategies

Advances in immunotherapy for osteosarcoma have shown promising results, with the use of monoclonal antibodies and immune checkpoint inhibitors. These strategies are aimed at targeting specific molecules and pathways involved in tumour immune evasion and promoting anti-tumour immune responses. Other emerging immunotherapeutic approaches include autophagy and pyroptosis induction, chimeric antigen receptor T-cell therapy, gadolinium-bisphosphonate nanoparticles and dendritic cell-based vaccines. Continued research into these emerging treatment strategies is essential for developing effective therapies for patients with high-grade osteosarcoma.