Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis

ESMO Open, Год журнала: 2024, Номер 9(2), С. 102220 - 102220

Опубликована: Янв. 21, 2024

Background

Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that time day (ToD) ICI administration could impact outcomes patients with cancer. The consistency ToD effects on efficacy awaits initial evaluation.

Materials and methods

This meta-analysis integrates progression-free survival (PFS) overall (OS) data from studies a defined ‘cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] an earlier progression or death according to ‘early' ‘late' ICIs were collected each report pooled.

Results

Thirteen involved 1663 (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial (5%), esophageal (4%). Most received anti-programmed protein 1 death-ligand (98%), small proportion also anti-cytotoxic T-lymphocyte-associated 4 (anti-CTLA-4) (18%). cut-offs 13:00 14:00 (i.e. median infusion time), six studies, 16:00 16:30 reported threshold weaker vaccination responses) seven studies. Pooled analyses revealed early groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) PFS 0.51, 0.42-0.61; compared late groups.

Conclusions

Patients selected metastatic cancers seemed largely benefit infusions, which is consistent circadian mechanisms in immune-cell functions trafficking. Prospective randomized trials are needed establish recommendations optimal timing ICI-based therapies.

Язык: Английский

---

Novel Approaches for Assessing Circadian Rhythmicity in Humans: A Review

Journal of Biological Rhythms, Год журнала: 2020, Номер 35(5), С. 421 - 438

Опубликована: Июль 23, 2020

The temporal organization of molecular and physiological processes is driven by environmental behavioral cycles as well self-sustained circadian oscillators. Quantification phase, amplitude, period, disruption oscillators essential for understanding their contribution to sleep-wake disorders, social jet lag, interindividual differences in entrainment, the development chrono-therapeutics. Traditionally, assessment human system, output SCN particular, has required collection long time series univariate markers such melatonin or core body temperature. Data were collected specialized laboratory protocols designed control influences on rhythmicity. These are time-consuming, expensive, not practical assessing status patients participants epidemiologic studies. Novel approaches parameters peripheral have been developed. They based machine learning mathematical model-informed analyses features extracted from 1 a few samples high-dimensional data, transcriptomes, metabolomes, long-term simultaneous recording activity, light exposure, skin temperature, heart rate vitro approaches. Here, we review whether these successfully quantify central indexed gold standard markers. Although several perform under entrained conditions when sleep occurs at night, methods either worse other shift work they assessed any than entrainment thus do yet know how robust are. hold promise medicine, chrono-therapeutics, chrono-epidemiology. There remains need validate against markers, individuals all sexes ages, patient populations, and, which displaced.

Язык: Английский

---

Circadian Rhythms, Disease and Chronotherapy

Journal of Biological Rhythms, Год журнала: 2021, Номер 36(6), С. 503 - 531

Опубликована: Сен. 22, 2021

Circadian clocks are biological timing mechanisms that generate 24-h rhythms of physiology and behavior, exemplified by cycles sleep/wake, hormone release, metabolism. The adaptive value is evident when internal body daily environmental mismatched, such as in the case shift work jet lag or even mistimed eating, all which associated with physiological disruption disease. Studies animal human models have also unraveled an important role functional circadian modulating cellular organismal responses to cues (ex., food intake, exercise), pathological insults (e.g. virus parasite infections), medical interventions medication). With growing knowledge molecular underlying pathophysiology, it becoming possible target for disease prevention treatment. In this review, we discuss recent advances research potential therapeutic applications take patient into account treating

Язык: Английский

---

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy

Cancers, Год журнала: 2022, Номер 14(20), С. 5071 - 5071

Опубликована: Окт. 17, 2022

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes the environment. These are controlled by a very complex molecular mechanism, circadian clock, that regulates expression of multiple genes ensure right functioning body. An individual’s system is altered during aging, this related numerous age-associated pathologies other alterations could contribute development cancer. Nowadays, there an increasing interest understanding how rhythms be used treatment Chronotherapy aims understand impact biological have on response therapy optimize its action, maximize health benefits minimize possible adverse effects. Clinical trials so far confirmed optimal timing with chemo or immunotherapies decrease drug toxicity increase efficacy. Instead, chronoradiotherapy seems treatment-related symptoms rather than tumor progression patient survival. In addition, potential therapeutic targets within clock also been identified. Therefore, results application chronotherapy cancer until now challenging, feasible, applied clinical practice improve without additional costs. However, different limitations variables such as age, sex, chronotypes, among others, should overcome before can really put into practice.

Язык: Английский

---

The circadian clock and diseases of the skin

FEBS Letters, Год журнала: 2021, Номер 595(19), С. 2413 - 2436

Опубликована: Сен. 18, 2021

Organisms have an evolutionarily conserved internal rhythm that helps them anticipate and adapt to daily changes in the environment. Synchronized light–dark cycle with a period of around 24 hours, timing circadian clock is set by light‐triggering signals sent from retina suprachiasmatic nucleus. Other inputs, including food intake, exercise, temperature, also affect clocks peripheral tissues, skin. Here, we review intricate interplay between core network fundamental physiological processes skin such as homeostasis, regeneration, immune‐ stress responses. We illustrate effect feeding time on functions, previously overlooked area research. then discuss works relate its disruption diseases, cancer, sunburn, hair loss, aging, infections, inflammatory wound healing. Finally, highlight promise medicine for disease prevention management.

Язык: Английский

---

tauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 7, 2024

As the circadian clock regulates fundamental biological processes, disrupted clocks are often observed in patients and diseased tissues. Determining time of patient or tissue focus is essential medicine research. Here we present tauFisher, a computational pipeline that accurately predicts from single transcriptomic sample by finding correlations between rhythmic genes within sample. We demonstrate tauFisher's performance adding timestamps to both bulk single-cell samples collected multiple types experimental settings. Application tauFisher at cell-type level RNAseq dataset mouse dermal skin implies greater phase heterogeneity may explain dampened rhythm collective core gene expression immune cells compared fibroblasts. Given its robustness generalizability across assay platforms, setups, types, as well potential application data analysis, promising tool facilitates

Язык: Английский

---

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

Molecular Therapy — Methods & Clinical Development, Год журнала: 2020, Номер 18, С. 335 - 344

Опубликована: Июнь 10, 2020

Chronic administration of drugs leads to the activation compensatory mechanisms that may inhibit some their activity and induce unwanted toxicity. These are an obstacle for maintaining a sustainable effect many chronic medications. Pathways adapt burden induced by drugs, whether or not related underlying disease, can lead partial complete loss effect. Variability characterizes biological systems manifests itself as large intra- inter-individual differences in response drugs. Circadian rhythm-based chronotherapy is further associated with variability responses noted among patients. This paper reviews current knowledge regarding medications range variabilities have been described responses. Establishment personalized platform overcoming these prohibitive presented model ensuring long-term sustained medication effects. novel implements signatures individualized circadian rhythms preventing opposing drug administration. Compensatory activated toward chronically administered obstacles effects While body initially respond beneficial way, intrinsic adaptation drug, The de novo resistance attributed, cases, signaling pathways other cellular pathways. Many currently used small-molecule aimed at inhibition specific pathway. engage tolerance drug.1Gurevich E.V. Gurevich V.V. Beyond traditional pharmacology: new tools approaches.Br. J. Pharmacol. 2015; 172: 3229-3241Crossref PubMed Scopus (4) Google Scholar In activate promote exacerbation disorder cause side use agents, including antibodies, recombinant hormones, gene transfer-based cell-based technologies, was expected overcome obstacles.1Gurevich However, also be developed modalities. Combinations treatments target multiple simultaneously proposed method issues. Treatment-induced toxicity combinations inability continuous pharmacodynamically effective doses targeted require intermittent regimens.2Lopez J.S. Banerji U. Combine conquer: challenges therapy early phase trials.Nat. Rev. Clin. Oncol. 2017; 14: 57-66Crossref (110) data on potential deleterious role chronotherapy. establishment way presented. Partial result upon One-third patients rheumatoid arthritis (RA) show inadequate primary anti-tumor necrosis factor (TNF)-based drugs.3Gottenberg J.E. Brocq O. Perdriger A. Lassoued S. Berthelot J.M. Wendling D. Euller-Ziegler L. Soubrier M. Richez C. Fautrel B. et al.Non-TNF-targeted biologic vs second anti-TNF treat insufficient first drug: randomized clinical trial.JAMA. 2016; 316: 1172-1180Crossref (105) Several were underlie this non-responsiveness.4Khoury T. Ilan Y. Introducing patterns immune system immunomodulatory agents: improving therapies.Front. Immunol. 2019; 10: 2726Crossref (1) Some studies report efficacy up 48% patients.5Fafá B.P. Louzada-Junior P. Titton D.C. Zandonade E. Ranza R. Laurindo I. Peçanha Ranzolin Hayata A.L. Duarte al.BIOBADABRASILDrug survival causes discontinuation ankylosing spondylitis compared arthritis: analysis from BIOBADABRASIL.Clin. Rheumatol. 34: 921-927Crossref (26) Scholar,6Souto Maneiro J.R. Gómez-Reino J.J. Rate therapies systematic review meta-analysis registries health care databases.Rheumatology (Oxford). 55: 523-534PubMed Anti-TNF RA 47 months.5Fafá overall 10-year retention rate first-line agents 23%.7Biggioggero Favalli E.G. Ten-year treatment inflammatory arthritides.Drug Dev. Res. 2014; 75: S38-S41Crossref (0) Scholar,8Kalden Schulze-Koops H. Immunogenicity TNF inhibitors: implications treatment.Nat. 13: 707-718Crossref (77) A anti-TNFs occurs 40% bowel disease.9Ben-Horin Kopylov Chowers Optimizing disease.Autoimmun. 24-30Crossref (198) secondary response, following initial effect, 25%–61% patients.10Gisbert J.P. Panés Loss requirement infliximab dose intensification Crohn's disease: review.Am. Gastroenterol. 2009; 104: 760-767Crossref (463) Scholar, 11Billioud V. Sandborn W.J. Peyrin-Biroulet need adalimumab 2011; 106: 674-684Crossref (263) 12Ma Huang Fedorak D.K. Kroeker K.I. Dieleman L.A. Halloran R.N. disease outpatients treated earlier escalation infliximab: real life cohort study.J. Colitis. 8: 1454-1463Abstract Full Text PDF Inhibitors angiotensin-converting enzyme angiotensin II type 1 receptor hypertension; however, they increase plasma renin activity.13Barrios Escobar Aliskiren management hypertension.Am. Cardiovasc. Drugs. 2010; 349-358Crossref (12) heart failure, modest renin-angiotensin inhibitors attributed ability escape suppression via potentiation endogenous vasoactive peptides.14Packer McMurray J.J.V. Importance peptides broadening failure.Lancet. 389: 1831-1840Abstract (29) similarly neuro-endocrine circuits obesity.15van der Klaauw A.A. Neuropeptides obesity metabolic disease.Clin. Chem. 2018; 64: 173-182Crossref (14) Peroxisome proliferator-activated gamma (PPARγ) thiazolidinediones (TZDs), which improve insulin sensitivity reducing lipogenesis liver. hepatocyte-specific PPARγ counterbalance positive therapeutic actions systemic delivery TZDs.16Wolf Greenstein Majumdar N. Yang Subbaiah P.V. Kineman R.D. Cordoba-Chacon Hepatocyte-specific, PPARγ-regulated steatosis adult mice.J. Endocrinol. 232: 107-121Crossref relevant degree neurological GABAA receptors mediate "tonic" form depends detection GABA extrasynaptic receptors. process dentate granule cells modulated neurosteroids, undergo changes hormonal status stress. tonic currents exert paradoxical excitatory depolarization neurons network leading polarization thalamocortical neurons. Tonic increased models focal epilepsy, due change prevents seizure generation. Drugs potentiate currents, antiepileptic effect.17Walker M.C. Kullmann D.M. Noebels J.L. Avoli Rogawski M.A. Olsen R.W. Delgado-Escueta A.V. receptor-mediated epilepsy. Jasper's Basic Mechanisms Epilepsies. 4th edition. National Center Biotechnology Information [US], 2012https://doi.org/10.1093/med/9780199746545.003.0009Crossref imaging features drug-resistant epilepsy idiopathic generalized tonic-clonic hippocampal functional connectivity impaired correlates duration. contrast, drug-sensitive shows enhancement, marker identify predict resistance.18Wang Z. Wang X. Rong Xu Zhang Impaired resistant, seizures.Neuroreport. 30: 700-706Crossref (3) Dopamine depletion putamen linked Parkinson's while pathology it part mechanism. Patients mild-moderate studied after overnight dopamine replacement washout showed connectivity, both cerebellum motor cortex (M1). Increased cerebellar study correlated improved performance, M1 predicted poorer performance. Following standard levodopa, performance improved, along reduced putamen-cerebellar connectivity. reflects pathological harmful mechanism brain.19Simioni A.C. Dagher Fellows L.K. striatal-cerebellar disease.Neuroimage 54-62Crossref anti-malignant development resistance. Tumor regimens activating alternative growth Current methods targeting non-overlapping attempt generate synergism.20Huang H.C. Mallidi Liu Chiang C.T. Mai Goldschmidt Ebrahim-Zadeh Rizvi Hasan Photodynamic synergizes irinotecan outcomes pancreatic cancer.Cancer 76: 1066-1077Crossref (47) Cancer patient's genetic background or, alternatively, acquired tumors more sensitive part, micro-clonality/micro-genetic heterogeneity tumors.21Rueff Rodrigues A.S. resistance: brief overview viewpoint.Methods Mol. Biol. 1395: 1-18Crossref (42) Protein kinase-directed cancer only transient most Resistance develops within 2 years, mutations kinase feedback loops bypass compensate inhibited kinases.22Mancini Yarden Mutational level anti-cancer inhibitors.Semin. Cell 50: 164-176Crossref (20) regulation signaling. emergence leukemia, melanoma, lung breast similar mutations. addition mutations, results alternative/compensatory being activated.23Rosenzweig S.A. Acquired tyrosine kinases.Adv. 138: 71-98Crossref (17) Drug attenuated alterations target, steric interference, activity, conformational changes. It phenotype switching.24Murray B.W. Miller Durability therapies—a perspective resistance.Mol. Ther. 1975-1984Crossref phosphatidylinositol 3-kinase (PI3K)/phosphatase tensin homolog (PTEN)/AKT afford (RTK) anti-HER2 monoclonal antibodies (mAbs) has modeled. dynamic pathway sensitivity-to-resistance transition. tested human ovarian carcinoma cell lines, using combinatorial RTK, PTEN, PI3K enzymes resistance.25Goltsov Faratian Langdon S.P. Bown Goryanin Harrison D.J. PI3K/PTEN/AKT inhibition.Cell. Signal. 23: 407-416Crossref (19) include second- third-generation block oncogenic routes, mAbs.22Mancini combined PIK-75, inhibitor PI3K/AKT pathway, vemurafenib, inhibits mitogen-activated protein (MAPK) pathways, overcomes advanced melanomas. miR-126 synergistic when included triple combination alongside PIK-75 vemurafenib.26Pedini F. De Luca G. Felicetti Puglisi Boe Arasi M.B. Fratini Mattia Spada Caporali al.Joint action MAPK/PI3K against metastatic melanoma.Mol. 1836-1854Crossref (2) kinase, MET, upregulated over-activated glioblastoma (GBM). anti-MET frequently occurs. proteins altered MET inhibitor-resistant GBM, mammalian rapamycin (mTOR), fibroblast (FGFR1), epidermal (EGFR), signal transducer activator transcription 3 (STAT3), cyclooxygenase (COX-2). Simultaneous one promotes death proliferation resistant cells.27Cruickshanks Hine Gibert Yuan Oxford Grello Pahuski Dube Guessous al.Discovery exploitation glioblastoma.Clin. 25: 663-673Crossref (13) three cetuximab, trastuzumab (an mAb), osimertinib, onset osimertinib.28Romaniello Mazzeo Mancini Marrocco Noronha Kreitman Srivastava Ghosh Lindzen Salame T.M. al.A approved osimertinib blocking pathways.Clin. 24: 5610-5621Crossref Anti-cancer single limited tumor's meet its energy demands. metabolism-targeting face mechanisms. propranolol dichloroacetate attenuates tumor metabolism mTOR signaling, colony formation, induces apoptosis.29Lucido Miskimins W.K. Vermeer P.D. Propranolol glucose dependence HNSCC.Cancers (Basel). 476Crossref antiangiogenic upregulation compensatory/alternative angiogenesis, midst anti-angiogenic environment.30Pinto M.P. Sotomayor Carrasco-Avino Corvalan A.H. Owen G.I. Escaping therapy: strategies employed cells.Int. Sci. 17: 1489Crossref Scholar,31Gacche Assaraf Y.G. Redundant angiogenic resistance.Drug Resist. Updat. 36: 47-76Crossref (28) relative redundancy proangiogenic factors anti-VEGF agents. Dose intensity schedules impact Higher greater stimulation decreases mechanisms.32Sharan Woo Systems pharmacology approaches optimization therapies: opportunities.Front. 6: 33Crossref (9) computational modeling, based circulating biomarkers pharmacodynamics (PD), utilized attenuate resistance.32Sharan Pancreatic ductal adenocarcinoma (PDAC) chemoresistance pathways.33Adamska Elaskalani Emmanouilidi Kim Abdol Razak N.B. Metharom Falasca Molecular cancer.Adv. Regul. 68: 77-87Crossref (23) nanoliposomal gemcitabine-refractory ATP-binding cassette G2 (ABCG2) transporter-mediated efflux cells. suggested benzoporphyrin derivative-based photodynamic (PDT), photochemical cytotoxic modality, apoptotic reduce ABCG2 expression, thereby increasing intracellular levels tumor. animal models, PDT subclinical synergistically growth.20Huang adaptive abiraterone limits castration-resistant prostate cancer. Cabozantinib enhances mechanisms, IGFIR activation.34Wang Christie Bowden Lee G.S. Kantoff P.W. Sweeney C.J. abiraterone's phosphorylation anti-prostate activity.Clin. 21: 5578-5587Crossref major unrelated sometimes serious calcineurin cyclosporine tacrolimus immunosuppressive nephrotoxicity. resulting renal damage tubular death, pro-fibrotic effects, inflammation. pro-inflammatory JAK2/STAT3 TAK1/JNK/AP-1 TLR4/Myd88/IRAK unfolded nuclear κB (NF-κB) expression.35González-Guerrero Ocaña-Salceda Berzal Carrasco Fernández-Fernández Cannata-Ortiz Egido Ortiz Ramos A.M. Calcineurin recruit kinases JAK2 JNK, TLR UPR NF-κB-mediated kidney cells.Toxicol. Appl. 2013; 272: 825-841Crossref (18) Antipsychotic diabetes inhibiting muscle cells, hepatocytes, adipocytes free fatty acid inflammation, thus inducing direct apoptosis β cells.36Chen X.F. Shao Chen Deng antipsychotic drug-induced diabetes.Front. Neurosci. 11: 643Crossref Antipsychotic-induced movement disorders, antipsychotic-induced parkinsonism tardive dyskinesia, well-described Genes susceptibility modifier genes determine expression sub-phenotypes severity, progression striatal loss.37Greenbaum Lerer Pharmacogenetics disorders resource better understanding genes.Front. Neurol. 27Crossref Overall, examples suggest use. characteristic seen medications.38Ilan Why microbiome so successful: randomness gut manipulation?.Clin. Exp. 12: 209-217Crossref (8) 39Ilan Randomness microtubule dynamics: error requires correction inherent plasticity required normal function?.Cell Int. 43: 739-748Crossref 40Ilan Generating randomness: making out disordering false order into one.J. Transl. Med. 49Crossref (7) unpredictable remains challenge designing regimens. Inter- intra-patient explain patient-to-patient drug.24Murray Differences than pharmacogenomics Diversity ethnic variances, manifest pharmacokinetics (PK) Pharmacogenomics differences.41Yasuda S.U. S.M. ethnicity drugs: focus studies.Clin. 2008; 84: 417-423Crossref (270) Inter-individual drug-metabolizing enzymes, transporters sites absorption, distribution, exposure tissue distribution then impacts toxicity.42Urquhart B.L. Tirona R.G. R.B. Nuclear transporters: interindividual drugs.J. 2007; 47: 566-578Crossref (300) Marked analgesic nonsteroidal anti-inflammatory described. represents associations between pain patient phenotypes genotypes.43Theken K.N. non-steroidal drugs.Prostaglandins Other Lipid Mediat. 139: 63-70Crossref Scholar,44Bruno Tacconelli Patrignani perspectives.Basic Toxicol. 114: 56-63Crossref (62) trial examining according genotype two COX SNPs, inhibitory celecoxib COX-2 induction genotype, rs689466 having inhibition.45Lee S.J. Park M.K. Shin D.S. Chun M.H. cyclooxygenase-2 polymorphism.Drug Des. Devel. 2727-2736Crossref P-glycoprotein transporter expressed blood-brain barrier (BBB), brain. function BBB unpredictability brain.46Bauer Tournier Langer Imaging determinant central nervous drugs.Clin. 105: 1061-1064Crossref (5) Similarly, albuminuria-lowering marked previous albuminuria random true variation treatment. No correlation on- off-treatment observed placebo arm, shown There same individual re-exposed dose, suggesting

Язык: Английский

---

New Insights Into Cancer Chronotherapies

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Дек. 13, 2021

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances circadian rhythm cancers are closely related. clock genes differentially expressed many tumors, accelerate development progression tumors. In addition, tumor tissues exert varying compared normal due resetting altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit timing rhythms achieve higher efficacy mild toxicity. Due interpatient differences functions, our findings advocate an individualized precision approach chronotherapy. Herein, we review specific association between cancers. focus on chronotherapies personalized biomarkers The understanding will provide a rationale more effective clinical

Язык: Английский

---

Chronoradiobiology of Breast Cancer: The Time Is Now to Link Circadian Rhythm and Radiation Biology

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1331 - 1331

Опубликована: Янв. 25, 2022

Circadian disruption has been linked to cancer development, progression, and radiation response. Clinical evidence date shows that circadian genetic variation time of treatment affect response toxicity for women with breast cancer. At the molecular level, there is interplay between clock regulators such as PER1, which mediates ATM p53-mediated cell cycle gating apoptosis. These alterations may govern aggressive phenotypes, outcomes, Exploiting various mechanisms enhance therapeutic index by decreasing toxicity, increasing disease control, improving outcomes. We will review body's natural rhythms gene-regulation while exploring preclinical clinical implicates chronobiological disruptions in etiology discuss radiobiological principles regulation DNA damage responses. Lastly, we present potential rational approaches target pathways improve outcomes Understanding implications optimal timing ways entrain biology light, diet, agents like melatonin provide an avenue enhancing radiotherapy.

Язык: Английский

---

Sex differences and sex bias in human circadian and sleep physiology research

eLife, Год журнала: 2022, Номер 11

Опубликована: Фев. 18, 2022

Growing evidence shows that sex differences impact many facets of human biology. Here we review and discuss the on circadian sleep physiology, uncover a data gap in field investigating non-visual effects light humans. A virtual workshop biomedical implications physiology led to following imperatives for future research: i) design research be inclusive accessible; ii) implement recruitment strategies lead sex-balanced sample; iii) use visualization grasp effect sex; iv) statistical analyses include as factor and/or perform group by sex, where possible; v) make participant-level open available facilitate meta-analytic efforts.

Язык: Английский

---