Side Effects Of Cancer Treatment Research Articles

Chiisanoside from the Leaves of Acanthopanax sessiliflorus Can Resist Cisplatin-Induced Ototoxicity by Maintaining Cytoskeletal Homeostasis and Inhibiting Ferroptosis.

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity of Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated the active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology and activity screening determined that chiisanoside (CSS) plays a crucial role in combating CIO. Transcriptomics combined with network pharmacology analysis and experiments revealed that CSS activates the Dock1/PIP5K1A pathway to suppress the actin-severing protein gelsolin, protecting hair cells from cisplatin-induced cytoskeleton damage. CSS also activates the SLC7A11/GPX4 pathway via TGFBR2, reducing lipid peroxidation and intracellular iron accumulation to suppress cisplatin-induced ferroptosis. This study discovers that the major component CSS in A. sessiliflorus leaves reverses CIO by regulating actin homeostasis via Dock1 and inhibiting ferroptosis through TGFBR2, providing a theoretical basis for expanding CIO treatment targets and related drug development.

A look into the cancer continuum for the development of a physical activity intervention: qualitative investigation of the physical activity experiences and preferences of female cancer survivors.

Clinical guidelines recommend cancer survivors (i.e., people with a cancer diagnosis) engage in regular physical activity (PA) during and post treatment, yet most do not. Additionally, PA promotion for cancer survivors has primarily focused on post treatment, calling for an understanding of PA promotion during treatment. This study explores the PA experiences and preferences of both in-treatment and post-treatment breast and gynecologic cancer survivors (BGCS) to inform the design of a PA intervention. Semi-structured interviews were conducted with postmenopausal women aged ≥ 50years, diagnosed with breast or gynecological cancer (stages 1-3), who were undergoing, or recently completed (12 to 24months) chemotherapy and/or primary treatment. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to explore themes. Participants (N = 26; Mage: 63.9years) had a breast (92.3%) and gynecologic (7.7%) cancer diagnosis and 46.2% (n = 12) were in treatment whereas 53.8% (n = 14) were post treatment. BGCS experienced several side effects of cancer treatment and both groups felt PA was an important goal. In-treatment BGCS focused on managing side effects (e.g., fatigue) and recognized energy fluctuated around treatments, making those periods less ideal for PA. In-treatment BGCS strongly endorsed a flexible, at-home intervention. Post-treatment BGCS emphasized recovery and relapse prevention, also favoring at-home, flexible interventions but showing greater interest towards support groups to aid with their recovery journey. Preferred activities included walking, dancing, and muscle-strengthening. Findings highlight the unique challenges postmenopausal BGCS face in participating in PA, especially in-treatment, emphasizing the importance of a tailored PA intervention.

Evaluation of the common skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments

Purpose The diversity of skin diseases in patients with malignancies leads to diagnostic difficulties and complicate cancer treatment. Furthermore, the increasing use of chemotherapy drugs and novel treatment regimens raises the risk of the development of various cutaneous side effects and the need for dermatologists during cancer management. We investigated the skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments. Methods Medical records of cancer patients evaluated in the Dermatology clinic between July 2018 and April 2023 were retrospectively reviewed. Results This study included 872 cancer patients, 374 females and 498 males. Acute myeloid leukaemia was the most common malignancy, followed by multiple myeloma and invasive ductal breast carcinoma. Graft versus host disease was observed in 89 (10.2%) patients after stem cell transplantation and radiodermatitis developed in 16 (1.8%) patients. Maculopapular drug eruption and hand foot syndrome were the most common cutaneous side effects of chemotherapy drugs. Capecitabine was the most common etiologic agent in hand foot syndrome. Cellulitis was the most frequent bacterial infection in cancer patients, whereas herpes zoster was the most frequent viral infection. Among the chemotherapy drugs that caused acneiform drug eruption, cetuximab and cytarabine were notable. Facial erythema was associated with cytarabine use in 27.3% of patients. Conclusion Identifying the common skin diseases in cancer patients and cutaneous side effects due to chemotherapy drugs may help to take preventive measures, develop specific and effective treatments, determine the most appropriate cancer treatment options, and increase patients’ compliance with cancer treatment.

A pilot randomized controlled trial of a virtual peer-support exercise intervention for female older adults with cancer

BackgroundRegular exercise can mitigate side effects of cancer treatment. However, only a small proportion of adults with cancer meet exercise guidelines, and older adults (> 65 years) are underrepresented in cancer rehabilitation research. Peer support facilitates health-promoting behaviours in general populations, but interventions merging exercise and peer support for older adults with cancer are not examined. The purpose of this study was to determine the feasibility and preliminary effectiveness of a virtual partner-based peer support exercise intervention for older adult female cancer survivors.MethodsOlder adult female cancer survivors with internet access and currently participating in < 150 min of moderate-vigorous physical activity per week were included in this study. Participants were matched with a partner and given a peer support guide, exercise guidelines, and a Fitbit Inspire©. In addition, intervention group dyads (AgeMatchPLUS) had weekly 1-h virtual sessions with a qualified exercise professional for 10 weeks. Dyads randomized to the control group (AgeMatch) independently supported their partner around exercise for 10 weeks. The primary outcome was feasibility, measured using retention and adherence rates. Secondary outcomes included exercise volume, social support, quality of life, physical function, and physical activity enjoyment. Descriptive statistics were used to report feasibility and an ANCOVA was used to explore between group differences on secondary outcomes at post-intervention (10 weeks post baseline) and post-tapering timepoints (14 weeks post baseline).ResultsEighteen participants (9 dyads; mean age 72 years (SD: 5.7 years)) were included in the pilot trial. Retention and adherence rates to the AgeMatchPLUS intervention were 100% and 95% respectively. All but one participant was satisfied with the quality of their peer match. Preliminary effects were seen between group, favouring AgeMatchPLUS for exercise-related social support post-intervention (effect size (d) = 0.27, 95% CI = 0,0.54) and physical activity enjoyment at post-tapering (d = 0.25, 95% CI = 0,0.52) and favouring the AgeMatch group for 30 s sit-to-stand repetitions at post-tapering (d = 0.31, 95% CI = 0.004, 0.57). No other effects were found.ConclusionsA virtual partner-based exercise intervention for older adults with cancer is feasible and shows preliminary effect benefits. Findings inform future trials aimed at increasing exercise in older adults with cancer.Trial registrationClinicaltrials.gov (ID: NCT05549479, date: 22/09/22).

The Effect of Quercetin on the Expression of miR-21 and miR-34a-5p on HeLa and Ca Ski Cell Lines

Background: Cervical cancer is the fourth most common cancer among women. In recent years, significant progress has been made in its treatment. Quercetin, a polyphenolic compound found in flavonoid-containing plants, is of interest due to its potential therapeutic effects. miR-21 plays a crucial role in cervical tumor metastasis by activating pathways related to invasion and migration, while miR-34a-5p is essential in regulating epithelial-to-mesenchymal transition and preventing increased cell proliferation and migration. The findings of this study could provide insight into the role of quercetin in cancer cells. Objectives: This study aims to investigate the effect of quercetin on the expression levels of miR-21 and miR-34a-5p in HeLa and Ca Ski cervical cancer cell lines. Methods: In this study, HeLa and Ca Ski cells were treated with quercetin. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry over a 48-hour period. Additionally, the effects of quercetin on the expression levels of miR-21 and miR-34a-5p were analyzed using qRT-PCR. Results: The study demonstrated that quercetin inhibited the viability of HeLa and Ca Ski cells and induced apoptosis in these cells. Quercetin suppressed cell viability with an IC50 of 102.9 μM for HeLa and 304.1 μM for Ca Ski cells after 48 hours. Quercetin down-regulated miR-21 in HeLa and Ca Ski cell lines by 2.5 ± 0.1 (P = 0.045) and 2.0 ± 0.2 (P = 0.016) fold, respectively. Additionally, miR-34a-5p increased by 3.3 ± 0.7 (P = 0.010) and 2.4 ± 0.8 (P = 0.047) fold after exposure to quercetin in HeLa and Ca Ski cell lines, respectively. Conclusions: Our study showed that quercetin has an anti-cervical cancer effect and can be used alongside standard therapies as a promising agent with fewer side effects in cervical cancer treatment.

Expansion of a bacterial operon during cancer treatment ameliorates drug toxicity.

Dose-limiting toxicities remain a major barrier to drug development and therapy, revealing the limited predictive power of human genetics. Herein, we demonstrate the utility of a more comprehensive approach to studying drug toxicity through longitudinal study of the human gut microbiome during colorectal cancer (CRC) treatment ( NCT04054908 ) coupled to cell culture and mouse experiments. 16S rRNA gene sequencing revealed significant shifts in gut microbial community structure during oral fluoropyrimidine treatment across multiple patient cohorts, in mouse small and large intestinal contents, and in patient-derived ex vivo communities. Metagenomic sequencing revealed marked shifts in pyrimidine-related gene abundance during oral fluoropyrimidine treatment, including enrichment of the preTA operon, which is sufficient for the inactivation of active metabolite 5-fluorouracil (5-FU). preTA + bacteria depleted 5-FU in gut microbiota grown ex vivo and the mouse distal gut. Germ-free and antibiotic-treated mice experienced increased fluoropyrimidine toxicity, which was rescued by colonization with the mouse gut microbiota, preTA + E. coli , or preTA -high CRC patient stool. Finally, preTA abundance was negatively associated with fluoropyrimidine toxicity in patients. Together, these data support a causal, clinically relevant interaction between a human gut bacterial operon and the dose-limiting side effects of cancer treatment. Our approach is generalizable to other drugs, including cancer immunotherapies, and provides valuable insights into host-microbiome interactions in the context of disease. One Sentence Summary: Gut microbial enzymes can be used to predict and prevent anticancer drug toxicity.

Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study.

Chemotherapy-induced cognitive impairment (CICI) is a well-recognized side effect of breast cancer treatment. However, prospective long-term evaluations of CICI using standardized neuropsychological tests are scarce. This prospective longitudinal cohort study investigated cognitive dysfunction and its impact on quality of life and everyday functioning in patients with breast cancer receiving first-line chemotherapy compared to patients with breast cancer without chemotherapy. Assessment occurred prior to chemotherapy, postchemotherapy (median 6 months), and 2-3 years later. We used standardized neuropsychological tests, questionnaires, and scales to assess patients' quality of life and functioning. Additionally, serum analysis for neurodegenerative markers and autoantibodies was conducted. We included n = 53 patients. Overall cognitive function declined statistically significantly (P = .046) postchemotherapy compared to control patients, mostly driven by a reduced figural memory (P = .011). Patients who received chemotherapy showed a greater reduction in quality of life (increased fatigue symptoms, P = .023; reduced Karnofsky index, P<.001); however, without a statistically significant effect on cognitive decline. The neurodegenerative markers Neurofilament light chain (NfL) and phosphorylated Neurofilament heavy chain (pNfH) increased statistically significantly (P<.001) postchemotherapy and pNfH correlated with overall cognitive function. After 2-3 years, both cognitive performance and quality of life were comparable between chemotherapy-treated and control patients. Our findings suggest that chemotherapy statistically significantly contributes to overall cognitive dysfunction in patients with breast cancer, which disappears after 2-3 years, indicating a recovery in both objectively measurable cognitive function and subjective quality of life. Future research should examine larger sample sizes and explore screening indicators, particularly pNfH.

Implementing a financial toxicity screening program.

275 Background: Financial toxicity (FT) is a well-documented negative side effect of cancer treatment. Routine screening can mitigate FT by proactively connecting at-risk patients to resources and counseling. Herein, we describe implementation of a FT screening quality improvement (QI) program. Methods: At a comprehensive cancer center, an interdisciplinary team explored options for implementation, with consideration for screening content, mechanism for delivery, and clinical workflow. Through consensus, the team agreed to use the 12-item COmprehensive Score for Financial Toxicity (COST) tool, a health-related social risk checklist, patient-self report of cost-related medication non-adherence, and a visual analog quality of life scale. Surveys were sent via portal every four months to patients on active treatment. The QI project was implemented on the breast, gastrointestinal, gynecologic, and thoracic services. COST scores ≤20 or any endorsed social risk (e.g., food, transportation) yielded a positive screen, and nurses placed a financial counseling referral, with counseling dispositions tracked. In March 2023, due to an influx of “unproductive” counseling dispositions (e.g., patient could not be contacted, patient no longer wanted help), machine learning models suggested reducing the screening threshold to COST scores ≤16 and limiting the social risk checklist to four items (food, transportation, medication, and housing insecurity). Results: From 06/2022-12/2023, 196,675 financial toxicity surveys were assigned to 78,289 unique patients: 38% (n=75,526) were completed by 45,003 patients. Of these, 56% have completed one survey, 26% have completed two surveys, and 18% have completed three or more. Since implementation, 9612 financial counseling referrals have been placed, yielding assistance with insurance selection and applications for assistance with co-payments, non-medical expenses, and out-of-pocket costs. During the QI project, several real-time workflow changes were made. On day 1, 519/1811 patients screened positive, yielding an overflow of counseling referrals: an additional question to allow patients to opt into referral, rather than generating an automatic referral, was then added: the following week, 136 referrals were generated. In September 2022, this opt-in was modified to allow patients to directly identify the areas in which they were seeking assistance (e.g., insurance counseling, out-of-pocket expenses). In 2024, the screening was reduced to two COST questions that had a 0.92 correlation with the full-tool. Conclusions: Routine FT screening is feasible during active treatment, although attention is needed to clinical workflows to ensure patients have access to the screening, nurses and other clinical staff are involved in the implementation, and referrals to resources are available for patients who screen positive. Future work will address cadence of delivery and outcomes of interventions.

Safety Evaluation of Carbon Dots in UM-UC-5 and A549 Cells for Biomedical Applications

Backgroung: The rising complexity and associated side effects of cancer treatments highlight the need for safer and more effective therapeutic agents. Carbon-based nanomaterials such as CDs have been gaining prominence for their unique characteristics, opening avenues for diverse applications such as fluorescence imaging, drug and gene transport, controlled drug delivery, medical diagnosis, and biosensing. Despite promising advancements in research, it remains imperative to scrutinize the properties and potential cytotoxicity of newly developed CDs, ensuring their viability for these applications. Methods: We synthesized four N-doped CDs through a hydrothermal method. Cell viability assays were conducted on A549 and UM-UC-5 cancer cells at a range of concentrations and incubation times, both individually and with the chemotherapeutic agent 5-fluorouracil (5-FU). Results: The obtained results suggest that the newly developed CDs exhibit suitability for applications such as bioimaging, as no significant impact on cell viability was observed for CDs alone.

Multisymptom Burden in Cancer Survivors: Benefits of Physical Activity

ABSTRACT In contrast with other leading causes of mortality, the cancer death rate in the United States continues to decline, reflecting improvements in prevention, screening, and treatment. Despite these advances, there has been limited development of strategies to counter the unwanted and debilitating effects associated with cancer and its treatments. Indeed, syndromes including cachexia, cardiotoxicity, fatigue, and mucositis among others plague cancer survivors, leading to poor life quality and premature mortality. The systemic nature of these impairments creates a strong rationale for treatment strategies to mitigate syndromes affecting cancer survivors. Currently, however, there are limited treatments approved by the US Food and Drug Administration to counter the debilitating side effects of cancer and cancer treatments. In noncancer clinical populations, physical activity is a well-established strategy to increase muscle mass, improve cardiovascular health, enhance energy levels, and promote gut health. Although physical activity programs are widely encouraged for cancer survivors, researchers are just beginning to understand the physiological basis of their positive effects and how they can be maximized for different cancer populations and treatments. This graphical review describes the benefits of physical activity and associated mechanisms for ameliorating select side effects of cancer and its therapeutics.

Prevalence of Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients and Its Effects on Quality of Life: A Survey Study

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment, leading to nerve damage and impairing patients' quality of life.Objective: To evaluate the prevalence of CIPN among cancer patients and its effects on their quality of life.Methods: A cross-sectional study was conducted at Allied Hospital, Pinum Cancer Hospital, and Aziz Fatima Hospital in Faisalabad, Pakistan. The study included 54 cancer patients (20 males, 34 females) aged 13-71 years, undergoing chemotherapy for at least six months. Patients were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy Induced Peripheral Neuropathy 20-item scale (EORTC-QLQ-CIPN20) and the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS). Data were analyzed using SPSS version 25, with descriptive statistics and chi-square tests performed to evaluate associations.Results: CIPN was prevalent in 90.7% of patients, with mild (59.3%), moderate (27.8%), and severe (3.7%) neuropathy levels. Neuropathy was significantly correlated with reduced quality of life (p = 0.663).Conclusion: CIPN is highly prevalent among cancer patients and significantly affects their quality of life. Early detection and management are crucial to mitigate these effects.

Cellular and Microbial In Vitro Modelling of Gastrointestinal Cancer.

Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision. Controlled environments allow researchers to isolate key variables, eliminate confounding factors and elucidate disease mechanisms more clearly. Technological progress has rapidly advanced model systems. Initially, 2D cell culture models explored fundamental cell interactions. The transition to 3D cell cultures and organoids enabled more life-like tissue architecture and enhanced intercellular interactions. Advanced bioreactor-based devices now recreate the physicochemical environments of specific organs, simulating features like perfusion and the gastrointestinal tract's mucus layer, enhancing physiological relevance. These systems have been simplified and adapted for high-throughput research, marking significant progress. This review focuses on in vitro systems for modelling gastrointestinal tract cancer and the side effects of cancer treatment. While cell cultures and in vivo models are invaluable, our main emphasis is on bioreactor-based in vitro modelling systems that include the gut microbiome.

Cancer therapy-related salivary dysfunction.

Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.

Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.

This review explores the cardiovascular toxicity associated with cancer therapies, emphasizing the significance of the growing field of cardio-oncology. It aims to elucidate the mechanisms of cardiotoxicity due to radiotherapy, chemotherapy, and targeted therapies, and to discuss the advancements in human induced pluripotent stem cell technology (hiPSC) for predictive disease modeling. Recent studies have identified several chemotherapeutic agents, including anthracyclines and kinase inhibitors, that significantly increase cardiovascular risks. Advances in hiPSC technology have enabled the differentiation of these cells into cardiovascular lineages, facilitating more accurate modeling of drug-induced cardiotoxicity. Moreover, integrating hiPSCs into clinical trials holds promise for personalized cardiotoxicity assessments, potentially enhancing patient-specific therapeutic strategies. Cardio-oncology bridges oncology and cardiology to mitigate the cardiovascular side-effects of cancer treatments. Despite advancements in predictive models using hiPSCs, challenges persist in accurately replicating adult heart tissue and ensuring reproducibility. Ongoing research is essential for developing personalized therapies that balance effective cancer treatment with minimal cardiovascular harm.

Erectile Dysfunction and Penile Bulb Dose Following Definitive Prostate Radiation Therapy

Background: Erectile dysfunction (ED) is a common side effect of prostate cancer treatment, affecting up to 50% of patients after radiation therapy. Objectives: This study aims to analyze the correlation between the dose received by the penile bulb (PB) and ED in men who underwent definitive radiation therapy for early-stage prostate cancer without androgen deprivation therapy. Methods: The study included 40 patients who received 3D conformal radiation therapy (3D-CRT) for localized prostate cancer and were reported to be potent before treatment, as determined by the International Index of Erectile Function (IIEF-15) questionnaire. The dose to the PB was measured using dose volume histograms (DVHs), and the IIEF-15 questionnaire was completed again 3 months after 3D-CRT. The Pearson correlation coefficient and linear regression test were used to examine the correlation between the ED score and PB doses. Statistical significance was considered if the P value was less than 0.05. Results: The mean age of the patients was 75.5 ± 5.70 years. The average ED score based on the questionnaire was 15 ± 10.55. Twenty percent of the patients had moderate ED, while 80% had mild ED (all patients reported a decrease in potency after 3D-CRT). However, the correlation between the ED score and the PB mean dose was not statistically significant. Conclusions: This study revealed ED in all prostate cancer patients after 3D-CRT, but no significant correlation was found between the dose received by the PB and radiotherapy-induced impotence.

Novel Synergistic Approach for Bioactive Macromolecules: Evaluating the Efficacy of Goat Placenta Extract in PEGylated Liposomes and Microspicules for Chemotherapy-Induced Hair Loss.

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy.

KLS-13019, a Novel Structural Analogue of Cannabidiol and GPR55 Receptor Antagonist, Prevents and Reverses Chemotherapy-Induced Peripheral Neuropathy in Rats.

Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential. Thus, neuropathic pain represents an area of critical unmet medical need, and novel classes of therapeutics with improved efficacy and safety profiles are urgently needed. The cannabidiol structural analog and novel antagonist of GPR55, KLS-13019, was screened in rat models of neuropathic pain. Tactile sensitivity associated with chemotherapy exposure was induced in rats with once-daily 1-mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for 1 week. Rats were then administered KLS-13019 or comparator drugs on day 7 in an acute dosing paradigm or days 7-10 in a chronic dosing paradigm, and mechanical or cold allodynia was assessed. Allodynia was reversed in a dose-dependent manner in the rats treated with KLS-13019, with the highest dose reverting the response to prepaclitaxel injection baseline levels with both intraperitoneal and oral administration after acute dosing. In the chronic dosing paradigm, four consecutive doses of KLS-13019 completely reversed allodynia for the duration of the phenotype in control animals. Additionally, coadministration of KLS-13019 with paclitaxel prevented the allodynic phenotype from developing. Together, these data suggest that KLS-13019 represents a potential new drug for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment with no known cure. The GPR55 antagonist KLS-13019 represents a novel class of drug for this condition that is a potent, durable inhibitor of allodynia associated with CIPN in rats in both prevention and reversal-dosing paradigms. This novel therapeutic approach addresses a critical area of unmet medical need.

Integrating lifestyle medicine into cancer care: A new paradigm.

179 Background: Amid rising global cancer rates and obesity-related cancer risks, oncology must blend traditional cancer treatments with evidence-based lifestyle medicine (LM) to enhance patient outcomes. LM—evidence-based interventions in nutrition, exercise, sleep, avoiding substances, and social connection —emerges as a critical tool in the care spectrum. ASCO and ACS guidelines incorporating lifestyle interventions are limited, and existing ones have notable implementation gaps. This study advocates for integration of LM into cancer care. Such interventions, supported by growing research, offer significant promise in reducing cancer treatment side effects and improving outcomes, highlighting an urgent need for their incorporation into oncological protocols. Methods: The Department of Preventive Medicine at Cleveland Clinic Abu Dhabi (CCAD) launched an LM program at the Oncology Institute. Oncologists refer to LM physicians who assess patients using an LM-validated questionnaire. Cardiometabolic risk factors: body composition, waist circumference, lipid profile, hemoglobin A1c, high-sensitivity CRP, liver function, and liver elastography are tested at baseline and 3 months. Patients receive personalized LM treatment by certified physicians, dieticians, physiatrists, and psychologists, aimed at reducing treatment side effects and enhancing cancer outcomes while improving cardiometabolic health. Follow-ups at 6 weeks and 3 months post-intervention ensure progress tracking and reassessment. Results: Initiated in January 2021, it began as a pilot program for breast cancer patients and has since expanded to all cancer patients. To date, it enrolled 425 patients, evidencing sustainability and acceptance within the patient community. Referral rates from oncologists have shown a steady increase, reflecting the program's growing credibility and utility. Patient satisfaction levels are reported to be high. Preliminary outcomes indicate improvements in both physical and psychological health metrics, suggestive of the program's comprehensive impact. Conclusions: The pioneering oncology LM program at CCAD established a transformative model that seamlessly integrates LM into traditional oncology care and acts as a bridge to survivorship. By ensuring sustained access to lifestyle interventions from the point of diagnosis through post-treatment, the program aligns with the latest research and ASCO/ACS guidelines, pioneering a new standard in cancer treatment. It can effectively address cardiometabolic risks, including obesity, and reduce treatment-related adverse outcomes. This program demonstrates the feasibility and a replicable global model, one that merges evidence-based lifestyle practices with standard oncological care to create a unified approach that could be adopted by healthcare systems worldwide, marking a significant step in the evolution of patient-centered cancer care.

Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.

This review highlights significant advancements in antibody-drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients.

Eight-year follow-up of patient-reported outcomes in patients with breast cancer participating in exercise studies during chemotherapy.

Numerous randomized controlled trials (RCTs) have shown beneficial exercise effects on fatigue, anxiety and depression and health-related quality of life (HRQoL) in breast cancer (BC) patients during and shortly after treatment. Here, we investigated the long-term effects of exercise during chemotherapy for BC on these outcomes. We invited participants of two highly comparable RCTs that investigated the effects of exercise (EX) (versus usual care (UC)) during chemotherapy in patients with non-metastatic BC (N = 357) to participate in an 8-year follow-up. In both trials, fatigue, anxiety and depression and HRQoL were assessed using the same questionnaires, at multiple timepoints. Linear mixed-effect models were used to compare study arms over time. In total, 156 participants (EX = 82; UC = 74) completed the follow-up questionnaires. EX reported comparable general (between-group difference 0.73, 95% confidence interval (- 0.35; 1.80), ES = 0.18) and physical fatigue (0.55 (- 0.55; 1.65), ES = 0.13), small but statistically significantly higher levels of anxiety (1.24 (0.47 to 2.00), ES = 0.39) and depression (1.10 (0.34; 1.85), ES = 0.38), significantly lower global HRQoL (- 5.99 (- 10.65; - 1.32), ES = 0.34) and comparable summary HRQoL (- 1.90 (- 4.70; 0.89), ES = 0.16) compared to UC. No long-term beneficial effects of exercise during chemotherapy on BC patients' fatigue, anxiety, depression or HRQoL were observed. The less favourable outcomes for mood and HRQoL that were observed 8years after participation in an exercise intervention may be explained by selective loss-to-follow-up. The results highlight the need to incorporate strategies that promote physical activity maintenance after participation in an exercise programme to also counteract long-term detrimental side effects of cancer treatment.