Single Therapy Research Articles

Nanobubble-mediated co-delivery of siTRIM37 and IR780 for gene and sonodynamic combination therapy against triple negative breast cancer

Gene therapy often fails due to enzyme degradation and low transfection efficiency, and single gene therapy usually cannot completely kill tumor cells. Several studies have reported that tripartite motif-containing protein 37 (TRIM37) plays a significant role in promoting the occurrence and development of triple negative breast cancer (TNBC). Herein, we constructed siTRIM37 and IR780 co-loaded nanobubbles (NBs) to achieve the combination of gene therapy and sonodynamic therapy (SDT) against TNBC. On the one hand, ultrasound irradiation causes siRNA@IR780 NBs rupture to produce ultrasound targeted NB destruction effect, which promotes the entry of IR780 and siTRIM37 into cells, increasing the local concentration of IR780 and gene transfection efficiency. On the other hand, under the stimulation of ultrasound, IR780 generates reactive oxygen species to kill TNBC cells. Mechanism studies reveal that TRIM37 is an anti-apoptotic gene in TNBC, and inhibiting TRIM37 expression can induce cell death through the apoptotic pathway. And the combination of siTRIM37 and SDT can aggravate the degree of apoptosis to increase cell death. Therefore, siRNA@IR780 NBs-mediated combination therapy may provide a new treatment approach for TNBC in the future.

Analgesic effect of dance movement therapy: An fNIRS study

ObjectiveThis study aims to explores the physiological and psychological mechanisms of exercise-induced hypoalgesia (EIH) by combining the behavioral results with neuroimaging data on changes oxy-hemoglobin (HbO) in prefrontal cortex (PFC). MethodsA total of 97 healthy participants were recruited and randomly divided into three groups: a single dance movement therapy (DMT) group, a double DMT group, and control group. Evaluation indicators included the pressure pain threshold (PPT) test, the color-word stroop task (CWST) for wearing functional near-infrared spectroscopy (fNIRS), and the self-assessment manikin (SAM). The testing time is before intervention, after intervention, and one hour of sit rest after intervention. Results1) Repeated measures ANOVA revealed that, there is a time * group effect on the PPT values of the three groups of participants at three time points. After 30 min of acute dance intervention, an increase in the PPT values of 10 test points occurred in the entire body of the participants in the experimental group with a significant difference than the control group. 2) In terms of fNIRS signals, bilateral DLPFC and left VLPFC channels were significantly activated in the experimental group. 3) DMT significantly awakened participants and brought about pleasant emotions, but cognitive improvement was insignificant. 4) Mediation effect analysis found that the change in HbO concentration in DLPFC may be a mediator in predicting the degree of improvement in pressure pain threshold through dance intervention (total effect β = 0.7140). ConclusionIn healthy adults, DMT can produce a diffuse EIH effect on improving pressure pain threshold, emotional experience but only showing an improvement trend in cognitive performance. Dance intervention significantly activates the left ventrolateral and bilateral dorsolateral prefrontal cortex. This study explores the central nervous system mechanism of EIH from a physiological and psychological perspective.

640P Efficacy and safety of EPI-321, an investigational single dose epigenome editing therapy targeting D4Z4 in facioscapulohumeral Muscular Dystrophy (FSHD)

640P Efficacy and safety of EPI-321, an investigational single dose epigenome editing therapy targeting D4Z4 in facioscapulohumeral Muscular Dystrophy (FSHD)

Integrative Modeling of Signaling Network Dynamics Identifies Cell Type-Selective Therapeutic Strategies for FGFR4-Driven Cancers.

Oncogenic FGFR4 signaling represents a potential therapeutic target in various cancer types, including triple-negative breast cancer and hepatocellular carcinoma. However, resistance to FGFR4 single-agent therapy remains a major challenge, emphasizing the need for effective combinatorial treatments. Our study sought to develop a comprehensive computational model of FGFR4 signaling and to provide network-level insights into resistance mechanisms driven by signaling dynamics. An integrated approach, combining computational network modeling with experimental validation, uncovered potent AKT reactivation following FGFR4 targeting in triple-negative breast cancer cells. Analyzing the effects of cotargeting specific network nodes by systematically simulating the model predicted synergy of cotargeting FGFR4 and AKT or specific ErbB kinases, which was subsequently confirmed through experimental validation; however, cotargeting FGFR4 and PI3K was not synergistic. Protein expression data from hundreds of cancer cell lines was incorporated to adapt the model to diverse cellular contexts. This revealed that although AKT rebound was common, it was not a general phenomenon. For example, ERK reactivation occurred in certain cell types, including an FGFR4-driven hepatocellular carcinoma cell line, in which there is a synergistic effect of cotargeting FGFR4 and MEK but not AKT. In summary, this study offers key insights into drug-induced network remodeling and the role of protein expression heterogeneity in targeted therapy responses. These findings underscore the utility of computational network modeling for designing cell type-selective combination therapies and enhancing precision cancer treatment. Significance: Computational predictive modeling of signaling networks can decipher mechanisms of cancer cell resistance to targeted therapies and enable identification of more effective cancer type-specific combination treatment strategies.

Role of osimertinib plus brain radiotherapy versus osimertinib single therapy in EGFR-mutated Non-Small-Cell Lung Cancer with brain metastases: a meta-analysis and systematic review.

Single-agent osimertinib has improved outcomes in EGFR-mutated lung cancer patients with brain metastases (BMs), but still, 40% of them will experience an intracranial progression. We performed a systematic review to evaluate the role of brain radiotherapy upfront plus osimertinib. We evaluated articles comparing the use of osimertinib versus osimertinib plus brain radiotherapy. We included 897 patients from nine retrospective studies. Patients treated with combination therapy had an improvement in intracranial progression-free survival (HR 0.76; 95% CI 0.61-0.94) and overall survival (HR 0.56; 95% CI 0.36-0.87) with an acceptable safety profile. Osimertinib with upfront brain radiotherapy may be a suitable first-line treatment option for EGFR mutated patients with BMs at diagnosis. The main limitations of this analysis are the retrospective nature and the inability to control for a single variable of interest. Despite that, the combination of osimertinib and upfront brain radiotherapy is a treatment strategy that deserves further prospective trials.

Pulsed Field Ablation of Atrial Fibrillation: A Novel Technology for Safer and Faster Ablation.

Atrial fibrillation (AF), the most common arrhythmia, is associated with increased morbidity, mortality, and healthcare costs. Evidence indicates that rhythm control offers superior cardiovascular outcomes compared to rate control, especially when initiated early after the diagnosis of AF. Catheter ablation remains the single best therapy for AF; however, it is not free from severe complications and only a small percentage of AF patients in the Western world ultimately receive ablation. Ensuring that AF ablation is safe, effective, and efficient is essential to make it accessible to all patients. With the limitations of traditional thermal ablative energies, pulsed field ablation (PFA) has emerged as a novel non-thermal energy source. PFA targets irreversible electroporation of cardiomyocytes to achieve cell death without damaging adjacent structures. Through its capability to create rapid, selective lesions in myocytes, PFA presents a promising alternative, offering enhanced safety, reduced procedural times, and comparable, if not superior, efficacy to thermal energies. The surge of new evidence makes it challenging to stay updated and understand the possibilities and challenges of PFA. This review aims to summarize the most significant advantages of PFA and how this has translated to the clinical arena, where four different catheters have received CE-market approval for AF ablation. Further research is needed to explore whether adding new ablation targets, previously avoided due to risks associated with thermal energies, to pulmonary vein isolation can improve the efficacy of AF ablation. It also remains to see whether a class effect exists or if different PFA technologies can yield distinct clinical outcomes given that the optimization of PFA parameters has largely been empirical.

Modulatory Sedative Activity of Abrine on Diazepam in Thiopental Sodium Mediated Sleeping Mice: An In Vivo Approach with Receptor Binding Affinity of GABAergic Transmission

AbstractThe current study aims to assess the effects of abrine (ABR) in thiopental sodium (TS)‐induced sleeping mice and to explore the sedative impacts of the compound by using in vivo and in silico investigations. ABR (5 and 10 mg k−1g, i.p.) and diazepam (DZP) (2 mg k−1g, i.p.) were administered to the experimental animals either single or combined. TS (20 mg k−1g, i.p.) was administered to induce sleep, and latency with sleeping duration was observed for 3 h. The in silico investigation was conducted to predict the role of ABR in the gamma‐aminobutyric acid A (GABAA) receptor in the sleeping process and to evaluate pharmacokinetics and toxicity. Results showed that ABR (10 mg k−1g) significantly (p < 0.05) decreased the latency period (8.20 ± 1.85 min) and enhanced sleep duration (187.8 ± 8.87 min) in comparison with the control group. Additionally, the co‐treatments of ABR and DZP remarkably reduced the latency period (4.40 ± 0.24 min) and increased the sleeping duration (201.40 ± 5.89 min) compared to the single therapy. The molecular docking indicated that ABR has a binding affinity of −7.4 kcal/mol for the GABAA receptor. In conclusion, ABR provides strong sedative and synergistic efficacy on TS‐induced sleeping mice via the GABAergic system.

GSH responsive AuNRs@TFF nanotheranostic for NIR-II photoacoustic imaging-guided CDT/PTT synergistic cancer therapy

Gold nanorods (AuNRs) are important photothermal therapeutic agents; however, a single therapy does not achieve satisfactory outcomes, and the synthesis process often leads to the adsorption of cetyltrimethylammonium bromide on the surface of AuNRs, which reduces its biocompatibility. Natural polyphenols are abundant in natural plants and have good biocompatibility. The metal-polyphenol network is formed by the coordination of metal ions and polyphenols, which has good drug loading, surface adhesion, and biocompatibility. In this study, the metal-polyphenol network structure formed by a transition metal (iron) and natural polyphenol tannic acid was used to modify the surface of gold nanorods (AuNRs@TF). Additionally, the surfaces of AuNRs were modified using the targeted functional molecule mercapto folic acid (AuNRs@TFF). The constructed composite nanomaterials AuNRs@TFF has good biocompatibility and tumor targeting ability. Tannic acid‑iron degrades in the tumor microenvironment and releases iron ions that catalyze the Fenton reaction, thereby facilitating chemodynamic therapy. The good photo-thermal ability of AuNRs generate good photoacoustic signals to facilitate photoacoustic imaging mediation and enhances photothermal and chemodynamic therapy performance. This study expands on the application of AuNRs in the field of nanomedicine. The simple and effective design of AuNRs@TFF provides a strategy for the development of synergistic therapeutic agents for photothermal therapy and chemodynamic therapy.

A retrospective study of the safety and efficacy of clopidogrel versus aspirin monotherapy one year after coronary stent implantation

BackgroundThe ideal single antiplatelet therapy for long-term maintenance after coronary stenting remains uncertain. In a head-to-head comparison, we aimed to evaluate the efficacy and safety profile of aspirin and clopidogrel as monotherapies in this patient cohort.MethodWe reviewed 1044 patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES) at the Department of Cardiovascular Medicine, Jinshan Hospital of Fudan University, between January 2019 and December 2021 and completed a 12-month Dual Antiplatelet Therapy (DAPT) treatment. They were divided into two groups: 582 were assigned to the aspirin group (100 mg/day) and 422 to the clopidogrel group (75 mg/day). The primary endpoint was the composite cardiac death, ischemic stroke, myocardial infarction, and Bleeding Academic Research Consortium (BARC) bleeding type 3 or greater. Secondary endpoint events included all-cause death, ischemic stroke, myocardial infarction, bleeding (defined as a BARC type ≥ 2 bleeding), and gastrointestinal complications.ResultsAfter a mean observation period of 25 ± 8.4 months, the primary endpoint event occurred in 29 (6.8%) patients in the clopidogrel group and 30 (5.1%) in the aspirin group, with no difference between the two groups (P = 0.253). In BARC type 2 or greater bleeding events, there were 9 (1.5%) in the aspirin group compared to 7 (1.7%) in the clopidogrel group, with no difference between the two groups (P = 0.160).ConclusionAfter 12-month DAPT in Chinese patients undergoing DES implantation, aspirin monotherapy versus clopidogrel monotherapy showed no significant difference between the two drugs in terms of safety and efficacy in terms of hemorrhage, myocardial infarction, ischemic stroke, cardiac death, and bleeding with BARC type 2 or greater.

Evaluation of Bleeding Time after Dental Extractions during Uninterrupted Single or Dual Antiplatelet Treatment - A Comparative Study

Abstract Introduction: This study aimed to assess the duration of bleeding after dental extractions amongst subjects with uninterrupted single antiplatelet therapy and dual antiplatelet therapy (DAPT) and to compare the bleeding time after dental extractions amongst those subjects undergoing various antiplatelet therapies. Materials and Methods: Post-extraction bleeding time was categorised as within 30 min, within 1 h and within 24 h. The bleeding time in different categories was compared and analysed using Chi-square. The antiplatelet agents assessed were aspirin, clopidogrel, ticagrelor and a combination of aspirin with clopidogrel and ticagrelor. Results: Bleeding time was significantly higher in patients under DAPT, compared to those under single antiplatelet therapy, and with an increase in the number of teeth extracted, there was an increase in bleeding time. All cases with prolonged bleeding could be managed with local haemostatic measures. Discussion: Simple extraction can be undertaken safely in patients under single antiplatelet therapy, considering that local haemostatic measures are available for use in the setup to control bleeding if necessary. Patients under DAPT are better managed if the therapy is altered, as there was a definite increase in bleeding time in patients under DAPT after extraction.

Short-term Dual Therapy or Mono Therapy With Acetaminophen and Ibuprofen for Fever: A Network Meta-Analysis.

There is uncertainty whether acetaminophen and ibuprofen are similar in their effects and safety when used as single or dual (alternating or combined) therapies. To assess the comparative efficacy of acetaminophen, ibuprofen alone, alternating, or combined through a systematic review and network meta-analysis. Medline, Embase, and CENTRAL from inception to September 20, 2023. Randomized trials comparing acetaminophen, ibuprofen, both alternating, and both combined, for treating children with fever. Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model. We included 31 trials (5009 children). We found that combined (odds ratio [OR], 0.19; confidence interval [CI], 0.09-0.42) and alternating therapies (OR, 0.20; CI, 0.06-0.63) may be superior to acetaminophen, whereas ibuprofen at a high dose may be comparable (OR, 0.98; CI, 0.63-1.59) in terms of proportion of afebrile children at the fourth hour. These results were similar at the sixth hour. There were no differences between ibuprofen (low or high dose), or alternating, or combined with acetaminophen in terms of adverse events. We only evaluated the efficacy and safety during the first 6 hours. Dual may be superior to single therapies for treating fever in children. Acetaminophen may be inferior to combined or alternating therapies to get children afebrile at 4 and 6 hours. Compared with ibuprofen, acetaminophen was also inferior to ibuprofen alone at 4 hours, but similar at 6 hours. PROSPERO registration: CRD42016035236.

Prognostic factors after radical local therapy for oligo-recurrence of non-small cell lung cancer.

Oligo-recurrence refers to the presence of a limited number of metachronous recurrences that can be treated with radical local therapy, and most patients have a good prognosis. However, the clinical course after local therapy for oligo-recurrence of non-small cell lung cancer (NSCLC) varies, and the prognostic factors are unclear. The aim of this study was to elucidate the prognostic factors of patients with oligo-recurrence of NSCLC who underwent radical local therapy. Between 2004 and 2015, 901 patients who underwent complete resection for NSCLC were included. We defined oligo-recurrence as two or fewer recurrences and retrospectively examined the factors that affected post-recurrence survival in patients who underwent radical local therapy for oligo-recurrence. Recurrence was confirmed in 267 patients, and among them, 125 experienced oligo-recurrence. Eighty-five patients with oligo-recurrence received local therapy, and their 5-year post-recurrence survival rate was 42.8%. Multivariable analysis of the prognostic factors of these patients revealed that single recurrence (hazard ratio = 2.19, P = 0.005) and systemic therapy (hazard ratio = 1.75, P = 0.043) were significant favorable prognostic factors associated with post-recurrence survival. However, the presence or absence of epidermal growth factor gene mutations, which is generally a prognostic factor for NSCLC recurrence, did not affect the prognosis of these patients. The number of recurrences and receiving systemic therapy are important prognostic factors for patients with oligo-recurrence who undergo radical local therapy, and these patients have a particularly favorable prognosis.

Real-World Survival Outcomes of First-Line Therapies in Patients with Metastatic Clear Cell Renal Cell Carcinoma: A Retrospective Analysis from Two Centres in Saudi Arabia.

Background: Metastatic renal cell carcinoma (mRCC) represents a challenging condition characterised by poor prognosis and limited response to chemoradiotherapy. In this retrospective study, we compared the survival outcomes of first-line ICI regimens versus single-agent TKIs in patients with mRCC from two centres in Saudi Arabia. Methods: This study included 84 patients diagnosed with clear cell mRCC between January 2016 and December 2023. Patients were grouped based on treatment regimens. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier curves and Cox proportional hazards regression. Results: The median first-line PFS was 9.7 months (95% CI: 5.3-14.1) for the overall cohort, with no significant difference between the single-agent tyrosine kinase inhibitor (TKI) group (9.4 months; 95% CI: 6.4-12.4), combination ICI group (9.0 months; 95% CI: 0.0-24.9), and single-agent ICI group (21.2 months; 95% CI: 2.6-39.8; p = 0.591). The median OS for the overall cohort was 42.0 months (95% CI: 14.9-69.2), with the single-agent TKI group having a median OS of 33.3 months (95% CI: 0.0-71.7), the combination ICI group, 42.0 months (95% CI: 0.06-84.0), and the single-agent ICI group, 23.0 months (95% CI: 19.2-26.7; p = 0.73). In comparison, the ICI-based combination therapy group exhibited a higher ORR of 41.0% (95% CI: 26.3-57.8%), while the single-agent ICI group had an ORR of 20.0% (95% CI: 3.5-55.8%). Cox regression identified liver metastasis as a significant independent predictor of PFS (HR = 1.8, p = 0.043), while a lower Karnofsky Performance Status was a significant independent predictor of OS (HR = 3.5, p < 0.001). Conclusions: In real-world practice from Saudi Arabia, first-line, single-agent ICI therapy offers promising anti-tumour activity and non-inferior survival outcomes compared to standard ICI-based combinations and single-agent TKIs.

Magnetic Hyperthermia in Glioblastoma Multiforme Treatment.

Glioblastoma multiforme (GBM) represents one of the most critical oncological diseases in neurological practice, being considered highly aggressive with a dismal prognosis. At a worldwide level, new therapeutic methods are continuously being researched. Magnetic hyperthermia (MHT) has been investigated for more than 30 years as a solution used as a single therapy or combined with others for glioma tumor assessment in preclinical and clinical studies. It is based on magnetic nanoparticles (MNPs) that are injected into the tumor, and, under the effect of an external alternating magnetic field, they produce heat with temperatures higher than 42 °C, which determines cancer cell death. It is well known that iron oxide nanoparticles have received FDA approval for anemia treatment and to be used as contrast substances in the medical imagining domain. Today, energetic, efficient MNPs are developed that are especially dedicated to MHT treatments. In this review, the subject's importance will be emphasized by specifying the number of patients with cancer worldwide, presenting the main features of GBM, and detailing the physical theory accompanying the MHT treatment. Then, synthesis routes for thermally efficient MNP manufacturing, strategies adopted in practice for increasing MHT heat performance, and significant in vitro and in vivo studies are presented. This review paper also includes combined cancer therapies, the main reasons for using these approaches with MHT, and important clinical studies on human subjects found in the literature. This review ends by describing the most critical challenges associated with MHT and future perspectives. It is concluded that MHT can be successfully and regularly applied as a treatment for GBM if specific improvements are made.

Immunotherapy for advanced and recurrent malignant pleural mesothelioma.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting.

Optimal duration of dual antiplatelet therapy for minor stroke within 72 hours of symptom onset: a prospective cohort study

ObjectivesDespite the potential spillover effect, the optimal duration of dual antiplatelet therapy for minor stroke within 72 hours of symptom onset is still uncertain.MethodsSafety and Efficacy of Aspirin-Clopidogrel in Acute...

THE EFFECTIVENESS OF STEM CELL THERAPY IN MYOCARDIAL INFARCTION REVIEWED FROM UREUM, CREATININE AND KIDNEY HISTOPATHOLOGY LEVELS

This study aims to study the effectiveness of single placental stem cell therapy or cardiomyocyte combination in pigs experiencing myocardial infarction in terms of urea, creatinine and kidney organ histopathology values. A total of 9 pigs were divided int o three groups: without therapy (K1), single placental stem cell therapy (K2), and cardiomyocyte coculture combination therapy (K3). All pigs underwent circumflex artery ligation of the proximal coronary artery branch to stimulate cardiac ischemia and therapy was given after myocardial infarction and ST-elevation were formed. The pigs were then treated for eight weeks, euthanized and necropsied for kidney organ removal. The re sults showed a significant decrease in urea and creatinine values (P0.05) in K2 and K3 as compared to K1. Histopathology results showed a decrease in glomerular atrophy values (K2: 10.26±0.93 and K3: 12.44±1.21), tubular necrosis (K2: 13.67±3.76 and K3: 17.23±0.55), and tubular dilation (K2: 16.36±1.26 and K3: 18.03±1.76) and these values were significantly different than those observed in K1. It was concluded that the administration of placental stem cell therapy or combined with cardiomyocyte coculture could reduce urea, creatinine values, and improve kidney tissue histopathologically.

The role of collagen in joint disorders: Applications in orthopedics, rheumatology, and sports medicine

Joint diseases are prevalent in orthopedic, rheumatological, and sports medicine fields, significantly impacting patients' quality of life. Collagen, a primary component of connective tissues, has emerged as a therapeutic agent for these conditions. This article explores the applications of collagen in joint diseases, comparing oral and intra-articular administration, evaluating optimal dosages, assessing single versus long-term therapies, discussing side effects, and examining the benefits of hydrolyzed versus non-hydrolyzed collagen. Additionally, explore various sources of collagen and their respective advantages for patient care.

“All in one” lipid-polymer nanodelivery system for gene therapy of ischemic diseases

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Ecological and evolutionary dynamics to design and improve ovarian cancer treatment.

Ovarian cancer ecosystems are exceedingly complex, consisting of a high heterogeneity of cancer cells. Development of drugs such as poly ADP-ribose polymerase (PARP) inhibitors, targeted therapies and immunotherapies offer more options for sequential or combined treatments. Nevertheless, mortality in metastatic ovarian cancer patients remains high because cancer cells consistently develop resistance to single and combination therapies, urging a need for treatment designs that target the evolvability of cancer cells. The evolutionary dynamics that lead to resistance emerge from the complex tumour microenvironment, the heterogeneous populations, and the individual cancer cell's plasticity. We propose that successful management of ovarian cancer requires consideration of the ecological and evolutionary dynamics of the disease. Here, we review current options and challenges in ovarian cancer treatment and discuss principles of tumour evolution. We conclude by proposing evolutionarily designed strategies for ovarian cancer, with the goal of integrating such principles with longitudinal, quantitative data to improve the treatment design and management of drug resistance. KEY POINTS/HIGHLIGHTS: Tumours are ecosystems in which cancer and non-cancer cells interact and evolve in complex and dynamic ways. Conventional therapies for ovarian cancer inevitably lead to the development of resistance because they fail to consider tumours' heterogeneity and cellular plasticity. Eco-evolutionarily designed therapies should consider cancer cell plasticity and patient-specific characteristics to improve clinical outcome and prevent relapse.