Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview

Chan, Alexandre; Hertz, Daniel L.; Morales, Manuel; Adams, Elizabeth; Gordon, Sharon M.; Tan, Chia Jie; Staff, Nathan P.; Kamath, Jayesh; Oh, Jong-Ryool; Shinde, Shivani; Pon, Doreen; Dixit, Niharkia; D’Olimpio, James T.; Dumitrescu, C; Gobbo, Margherita; Kober, Kord M.; Mayo, Samantha; Pang, Linda; Subbiah, Ishwaria Mohan; Beutler, Andreas S.; Peters, Katherine B.; Loprinzi, Charles L.; Lustberg, Maryam B.

doi:10.1007/s00520-019-04987-8

Cited by 63 publications

(44 citation statements)

References 79 publications

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“…The copyright holder for this preprint this version posted June 19, 2020. ; https://doi.org/10.1101/2020.04.23.20076208 doi: medRxiv preprint 3 neuropathy 5 . While most of these genetic association findings did not reach genome-wide significance, candidate gene analyses in independent populations support the associations with ephrin receptor genes, FGD4, and ARHGEF10 6 . The primary goal in the current study was to conduct a meta-analysis with two cohorts of breast cancer patients (CALGB 40502 and CALGB 40101) to extend these genomic findings and further elucidate this complex phenotype.…”

Section: Introductionmentioning

confidence: 87%

Genome-Wide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy

Chua

Xiong

et al. 2020

Preprint

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Microtubule targeting agents (MTAs) are anticancer therapies commonly prescribed for breast cancer and other solid tumors. Sensory peripheral neuropathy (PN) is the major dose-limiting toxicity for MTAs and can limit clinical efficacy. The current pharmacogenomic study aimed to identify genetic variations that explain patient susceptibility and drive mechanisms underlying development of MTA-induced PN. A meta-analysis of genome-wide association studies (GWAS) from two clinical cohorts treated with MTAs (CALGB 40502 and CALGB 40101) was conducted using a Cox regression model with cumulative dose to first instance of grade 2 or higher PN. Summary statistics from a GWAS of European subjects (n = 469) in CALGB 40502 that estimated cause-specific risk of PN were meta-analyzed with those from a previously published GWAS of European ancestry (n = 855) from CALGB 40101 that estimated the risk of PN. Novel single nucleotide polymorphisms in an enhancer region downstream of sphingosine-1-phosphate receptor 1 (S1PR1 encoding S1PR1; e.g., rs74497159, βCALGB 40101 per allele log hazard ratio (95% CI) = 0.591 (0.254 - 0.928), βCALGB 40502 per allele log hazard ratio (95% CI) = 0.693 (0.334 - 1.053); PMETA = 3.62x10-7) were the most highly ranked associations based on P-values with risk of developing grade 2 and higher PN. In silico functional analysis identified multiple regulatory elements and potential enhancer activity for S1PR1 within this genomic region. Inhibition of S1PR1 function in iPSC-derived human sensory neurons shows partial protection against paclitaxel-induced neurite damage. These pharmacogenetic findings further support ongoing clinical evaluations to target S1PR1 as a therapeutic strategy for prevention and/or treatment of MTA-induced neuropathy.

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Section: Introductionmentioning

confidence: 87%

Genome-Wide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy

Chua

Xiong

et al. 2020

Preprint

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“…In addition to age, a number of other potential risk factors for CIPN development have been identified. These include the cumulative dose of a chemotherapeutic agent, genetic factors, a history of neuropathy before the start of chemotherapy (e.g., painful diabetic neuropathy or neuropathy due to viral infections), impaired renal function with reduced creatinine clearance, and smoking history [9,15,17,[28][29][30][31][32].…”

Section: Prevalence Of Cipn and Risk Factorsmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Sałat

2020

Pharmacol. Rep

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Background Despite the increasing knowledge of the etiology of neuropathic pain, this type of chronic pain is resistant to available analgesics in approximately 50% of patients and therefore is continuously a subject of considerable interest for physiologists, neurologists, medicinal chemists, pharmacologists and others searching for more effective treatment options for this debilitating condition. Materials and methods The present review article is the first of the two articles focused on chemotherapy-induced peripheral neuropathy (CIPN). Results CIPN is regarded as one of the most common drug-induced neuropathies and is highly pharmacoresistant. The lack of efficacious pharmacological methods for treating CIPN and preventing its development makes CIPN-related neuropathic pain a serious therapeutic gap in current medicine and pharmacotherapy. In this paper, the most recent advances in the field of studies on CIPN caused by platinum compounds (namely oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib are summarized. Conclusions The prevalence of CIPN, potential causes, risk factors, symptoms and molecular mechanisms underlying this pharmacoresistant condition are discussed.

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“…CIPN ranks among the most common non-hematological dose-limiting toxicities of the platinum and taxane compounds. CIPN is often a sensory-predominant symptom associated with numbness, tingling, and neuropathic pain, especially in the hands and feet [ 1 , 2 , 3 , 4 ]. CIPN can occur acutely during chemotherapy and may require a reduction in drug dosage or even the premature stoppage of a planned treatment course, potentially impairing the efficacy of oncological treatment and survival [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study

Adjei

Lopez

Schaid

et al. 2021

Cancers

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially permanent adverse effect of chemotherapeutic agents including taxanes such as paclitaxel and platinum-based compounds such as oxaliplatin and carboplatin. Previous studies have suggested that genetics may impact the risk of CIPN. We conducted genome-wide association studies (GWASs) for CIPN in two independent populations who had completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-CIPN20 assessments (a CIPN-specific 20-item questionnaire which includes three scales that evaluate sensory, autonomic, and motor symptoms). The study population N08Cx included 692 participants from three clinical trials (North Central Cancer Treatment Group (NCCTG) N08C1, N08CA, and N08CB) who had been treated with paclitaxel, paclitaxel plus carboplatin, or oxaliplatin. The primary endpoint for the GWAS was the change from pre-chemotherapy CIPN20 sensory score to the worse score over the following 18 weeks. Study population The Mayo Clinic Breast Disease Registry (MCBDR) consisted of 381 Mayo Clinic Breast Disease Registry enrollees who had been treated with taxane or platinum-based chemotherapy. The primary endpoint for the GWAS assessed was the earliest CIPN20 sensory score available after the completion of chemotherapy. In multivariate model analyses, chemotherapy regimen (p = 3.0 × 10−8) and genetic ancestry (p = 0.007) were significantly associated with CIPN in the N08Cx population. Only age (p = 0.0004) was significantly associated with CIPN in the MCBDR population. The SNP most associated with CIPN was rs56360211 near PDE6C (p =7.92 × 10−8) in N08Cx and rs113807868 near TMEM150C in the MCBDR (p = 1.27 × 10−8). Due to a lack of replication, we cannot conclude that we identified any genetic predictors of CIPN.

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Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview

Cited by 63 publications

References 79 publications

Genome-Wide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy

Genome-Wide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Genetic Predictors of Chemotherapy-Induced Peripheral Neuropathy from Paclitaxel, Carboplatin and Oxaliplatin: NCCTG/Alliance N08C1, N08CA and N08CB Study

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