Personalized Medicine in Cancer Pain Management

Background: Previous studies have documented pain as an important concern for quality of life (QoL) and one of the most challenging manifestations for cancer patients. Thus, cancer pain management (CPM) plays a key role in treating pain related to cancer. The aim of this systematic review was to investigate CPM, with an emphasis on personalized medicine, and introduce new pharmacogenomics-based procedures for detecting and treating cancer pain patients. Methods: This study systematically reviewed PubMed from 1990 to 2023 using keywords such as cancer, pain, and personalized medicine. A total of 597 publications were found, and after multiple filtering processes, 75 papers were included. In silico analyses were performed using the GeneCards, STRING-MODEL, miRTargetLink2, and PharmGKB databases. Results: The results reveal that recent reports have mainly focused on personalized medicine strategies for CPM, and pharmacogenomics-based data are rapidly being introduced. The literature review of the 75 highly relevant publications, combined with the bioinformatics results, identified a list of 57 evidence-based genes as the primary gene list for further personalized medicine approaches. The most frequently mentioned genes were CYP2D6, COMT, and OPRM1. Moreover, among the 127 variants identified through both the literature review and data mining in the PharmGKB database, 21 variants remain as potential candidates for whole-exome sequencing (WES) analysis. Interestingly, hsa-miR-34a-5p and hsa-miR-146a-5p were suggested as putative circulating biomarkers for cancer pain prognosis and diagnosis. Conclusions: In conclusion, this study highlights personalized medicine as the most promising strategy in CPM, utilizing pharmacogenomics-based approaches to alleviate cancer pain.

[1]  J. Mao,et al.  Effect of acupuncture versus usual care on sleep quality in cancer survivors with chronic pain: Secondary analysis of a randomized clinical trial , 2023, Cancer.

[2]  Tianzhuo Zhang,et al.  Label-free serum proteomics for the identification of the putative biomarkers of postoperative pain in patients with gastric cancer. , 2023, Molecular omics.

[3]  Anne W. Ndungu,et al.  The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions , 2023, Nature Genetics.

[4]  E. Bruera,et al.  Levorphanol as a Second Line Opioid in Cancer Patients Presenting to an Outpatient Supportive Care Center: An Open-Label Study. , 2023, Journal of pain and symptom management.

[5]  M. Janecki,et al.  Relationship between breakthrough cancer pain, background cancer pain and analgesic treatment – case series and review of the literature , 2022, Drugs in context.

[6]  L. Manchikanti,et al.  A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain , 2022, Pain and Therapy.

[7]  G. Toh,et al.  Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review , 2022, Journal of personalized medicine.

[8]  A. Maconi,et al.  Effects of Ultrasound-Guided Injection Combined with a Targeted Therapeutic Exercise in Breast Cancer Women with Subacromial Pain Syndrome: A Randomized Clinical Study , 2022, Journal of personalized medicine.

[9]  M. Shevtsov,et al.  Microstructural Properties of Brain White Matter Tracts in Breast Cancer Survivors: A Diffusion Tensor Imaging Study , 2022, Pathophysiology : the official journal of the International Society for Pathophysiology.

[10]  E. Lam,et al.  Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain , 2022, Science advances.

[11]  K. Ikeda,et al.  Genome-Wide Association Study Identifies Candidate Loci Associated with Opioid Analgesic Requirements in the Treatment of Cancer Pain , 2022, Cancers.

[12]  W. Maixner,et al.  Applying the Rapid OPPERA Algorithm to Predict Persistent Pain Outcomes among a Cohort of Women Undergoing Breast Cancer Surgery. , 2022, The journal of pain.

[13]  Li Yang,et al.  Genetic variations in UCA1, a lncRNA functioning as a miRNA sponge, determine endometriosis development and the potential associated infertility via regulating lipogenesis , 2022, PLoS ONE.

[14]  M. Miyashita,et al.  Machine learning models to detect social distress, spiritual pain, and severe physical psychological symptoms in terminally ill patients with cancer from unstructured text data in electronic medical records , 2022, Palliative medicine.

[15]  Yu Zhang,et al.  Knowledge, attitudes, and practices toward cancer pain management amongst healthcare workers (physicians, pharmacists, and nurses): a cross-sectional study from first-tier cities in China , 2022, Supportive Care in Cancer.

[16]  Huiping Hu,et al.  Clinical Observation of the Effects of Oral Opioid on Inflammatory Cytokines and Gut Microbiota in Patients with Moderate to Severe Cancer Pain: A Retrospective Cohort Study , 2022, Pain and Therapy.

[17]  A. Vannacci,et al.  STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways , 2022, Pharmaceutics.

[18]  Sebastian M. Armasu,et al.  Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota , 2022, The Pharmacogenomics Journal.

[19]  M. Invernizzi,et al.  Physical Exercise with or without Whole-Body Vibration in Breast Cancer Patients Suffering from Aromatase Inhibitor—Induced Musculoskeletal Symptoms: A Pilot Randomized Clinical Study , 2021, Journal of personalized medicine.

[20]  A. Casamassimi,et al.  PRDM12 in Health and Diseases , 2021, International journal of molecular sciences.

[21]  D. Yadav,et al.  Serum biomarkers for chronic pancreatitis pain patterns. , 2021, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.].

[22]  Shengli Yang,et al.  Practice, Knowledge, and Attitude of Health Care Providers regarding Cancer Pain Management: A National Survey , 2021, Pain research & management.

[23]  Xander M R van Wijk,et al.  Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid Treated Oncology Patients. , 2021, The oncologist.

[24]  L. O’Connor,et al.  Pain assessment and registration in medical oncology clinics: operationalised through the lens of health care professionals and patients , 2021, HRB open research.

[25]  S. Apisarnthanarax,et al.  Pancreas Cancer‐Associated Pain Management , 2021, The oncologist.

[26]  E. Bruera,et al.  Genetic Factors associated with Pain Severity, Daily Opioid Dose Requirement, and Pain Response among Advanced Cancer Patients receiving Supportive Care. , 2021, Journal of pain and symptom management.

[27]  P. Kantoff,et al.  Effectiveness of Electroacupuncture or Auricular Acupuncture vs Usual Care for Chronic Musculoskeletal Pain Among Cancer Survivors: The PEACE Randomized Clinical Trial. , 2021, JAMA oncology.

[28]  A. Caraceni,et al.  Oxycodone/Acetaminophen: The Tailoring Combination Treatment for Specific Clinical Profile of Opioid Well-Responsive Cancer Pain , 2021, Cancer management and research.

[29]  E. Ben-Arye,et al.  Effects of a patient-tailored integrative oncology intervention in the relief of pain in palliative and supportive cancer care , 2021, Journal of Cancer Research and Clinical Oncology.

[30]  K. Sangkuhl,et al.  Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy , 2021, Clinical pharmacology and therapeutics.

[31]  Kimberson Tanco,et al.  How to Measure Pain , 2020, Current Oncology Reports.

[32]  P. Goss,et al.  Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-limited Settings: a Randomized Controlled Trial. , 2020, The oncologist.

[33]  R. Autorino,et al.  Re: Olaparib for Metastatic Castration-resistant Prostate Cancer. , 2020, European urology.

[34]  R. Fumagalli,et al.  Genetics and Opioids: Towards More Appropriate Prescription in Cancer Pain , 2020, Cancers.

[35]  Xuezhong Zhou,et al.  Identification of herbal categories active in pain disorder subtypes by machine learning help reveal novel molecular mechanisms of algesia. , 2020, Pharmacological research.

[36]  P. Hoskin,et al.  Bayesian methods in palliative care research: cancer-induced bone pain , 2020, BMJ Supportive & Palliative Care.

[37]  H. Sakuma,et al.  Alexithymia in Family Caregivers of Advanced Cancer Patients Is Associated with High Personalized Pain Goal Scores: A Pilot Study. , 2020, Journal of palliative medicine.

[38]  A. Farmer,et al.  Gastrointestinal pain , 2020, Nature Reviews Disease Primers.

[39]  Katherine Webber,et al.  Validation of the Dutch version of the Breakthrough Pain Assessment Tool in Patients with Cancer. , 2019, Journal of pain and symptom management.

[40]  Virginia T. LeBaron,et al.  Leveraging Smart Health Technology to Empower Patients and Family Caregivers in Managing Cancer Pain: Protocol for a Feasibility Study , 2019, JMIR research protocols.

[41]  R. Xu,et al.  Predicting Persistent Opioid Use, Abuse and Toxicity Among Cancer Survivors. , 2019, Journal of the National Cancer Institute.

[42]  W. Beach,et al.  Patient-Initiated Pain Expressions: Interactional Asymmetries and Consequences for Cancer Care , 2019, Health communication.

[43]  E. Shaw,et al.  Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study , 2019, Human Genomics.

[44]  G. Yang,et al.  Genetic Variants Associated with Cancer Pain and Response to Opioid Analgesics: Implications for Precision Pain Management. , 2019, Seminars in oncology nursing.

[45]  L. Colvin Chemotherapy-induced peripheral neuropathy: where are we now? , 2019, Pain.

[46]  A. Dash,et al.  Ce-141-labeled DOTMP: A theranostic option in management of pain due to skeletal metastases. , 2019, Journal of labelled compounds & radiopharmaceuticals.

[47]  G. Botti,et al.  Multimodal approaches and tailored therapies for pain management: the trolley analgesic model , 2019, Journal of pain research.

[48]  A. Fiorelli,et al.  Cancer- and Non-cancer Related Chronic Pain: From the Physiopathological Basics to Management , 2019, Open medicine.

[49]  E. Kalso,et al.  CACNG2 polymorphisms associate with chronic pain after mastectomy , 2018, Pain.

[50]  D. Walsh,et al.  Acupuncture for Cancer Pain and Symptom Management in a Palliative Medicine Clinic , 2018, The American journal of hospice & palliative care.

[51]  T. Taguchi,et al.  Classification of acute pain trajectory after breast cancer surgery identifies patients at risk for persistent pain: a prospective observational study , 2018, Journal of pain research.

[52]  H. McLeod,et al.  Design and rational for the precision medicine guided treatment for cancer pain pragmatic clinical trial. , 2018, Contemporary clinical trials.

[53]  M. Johantgen,et al.  Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity Groups in Colorectal Cancer. , 2017, Journal of pain and symptom management.

[54]  F. Remião,et al.  Opioids and the Blood-Brain Barrier: A Dynamic Interaction with 
Consequences on Drug Disposition in Brain , 2017, Current neuropharmacology.

[55]  Aniwaa Owusu Obeng,et al.  Review of Opioid Pharmacogenetics and Considerations for Pain Management , 2017, Pharmacotherapy.

[56]  R. Freeman,et al.  Chemotherapy-induced peripheral neuropathy clinical trials , 2017, Neurology.

[57]  Diane D. Liu,et al.  Assessing the prognostic features of a pain classification system in advanced cancer patients , 2017, Supportive Care in Cancer.

[58]  G. Chahine,et al.  OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings , 2017, International journal of molecular sciences.

[59]  W. Liu,et al.  Multidimensional Treatment of Cancer Pain , 2017, Current Oncology Reports.

[60]  L. Balducci,et al.  Palliative Care of Cancer in the Older Patient , 2016, Current Oncology Reports.

[61]  E. Bruera,et al.  Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[62]  S. Kaasa,et al.  The rare Arg181Cys mutation in the μ opioid receptor can abolish opioid responses , 2016, Acta anaesthesiologica Scandinavica.

[63]  V. Fellman,et al.  Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation , 2016, Therapeutic drug monitoring.

[64]  I. Knezevic,et al.  The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients , 2016, Expert opinion on drug metabolism & toxicology.

[65]  A. Wolfson,et al.  Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy , 2016, Dermatology and Therapy.

[66]  S. Bhatnagar,et al.  Integrated pain and palliative medicine model. , 2016, Annals of palliative medicine.

[67]  M. Gitlin,et al.  Desmoid Tumors: A Review of the Literature and Pharmacologic Management , 2016, Journal of pain & palliative care pharmacotherapy.

[68]  B. Melichar,et al.  A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[69]  E. Bruera,et al.  A personalized approach to assessing and managing pain in patients with cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[70]  D. Westerling Pain and Other Symptoms in Cancer Survivors , 2014, Journal of pain & palliative care pharmacotherapy.

[71]  D. McGuire,et al.  MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy , 2014, Cancer.

[72]  L. Thabane,et al.  Impact of ABCB1 and CYP2B6 Genetic Polymorphisms on Methadone Metabolism, Dose and Treatment Response in Patients with Opioid Addiction: A Systematic Review and Meta-Analysis , 2014, PloS one.

[73]  Qingyuan Zhang,et al.  Indications of Clinical and Genetic Predictors for Aromatase Inhibitors Related Musculoskeletal Adverse Events in Chinese Han Women with Breast Cancer , 2013, PloS one.

[74]  Jennifer A. Haythornthwaite,et al.  Longitudinal analysis of pain in patients with metastatic prostate cancer using natural language processing of medical record text , 2012, J. Am. Medical Informatics Assoc..

[75]  E. Bruera,et al.  Achievement of personalized pain goal in cancer patients referred to a supportive care clinic at a comprehensive cancer center , 2012, Cancer.

[76]  Yu-ting Chen,et al.  UGT2B7 genetic polymorphisms are associated with the withdrawal symptoms in methadone maintenance patients. , 2012, Pharmacogenomics.

[77]  E. Bruera,et al.  Assessing Cancer Pain , 2012, Current Pain and Headache Reports.

[78]  R. Labianca,et al.  The Appropriate Treatment of Chronic Pain , 2012, Clinical Drug Investigation.

[79]  Bonnie Spring,et al.  Meta-analysis of psychosocial interventions to reduce pain in patients with cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  D. Tripathy,et al.  Differences in the prevalence and severity of side effects based on type of analgesic prescription in patients with chronic cancer pain. , 2011, Journal of Pain and Symptom Management.

[81]  B. Larsson,et al.  Individualized pharmacological treatment of oral mucositis pain in patients with head and neck cancer receiving radiotherapy , 2011, Supportive Care in Cancer.

[82]  X. Declèves,et al.  Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology. , 2011, Current pharmaceutical design.

[83]  R. Portenoy Treatment of cancer pain , 2011, The Lancet.

[84]  Cinzia Brunelli,et al.  Multiple Loci Modulate Opioid Therapy Response for Cancer Pain , 2011, Clinical Cancer Research.

[85]  D. Walsh,et al.  Opioid and Adjuvant Analgesics: Compared and Contrasted , 2011, The American journal of hospice & palliative care.

[86]  F. Musshoff,et al.  Pharmacogenetics in palliative care. , 2010, Forensic science international.

[87]  K. Fried,et al.  Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2. , 2010, Genome research.

[88]  B. Fitzgerald,et al.  Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: a retrospective, outcomes-based survey. , 2010, Current oncology.

[89]  E. Tan,et al.  The influence of ATP-binding cassette sub-family B member -1 (ABCB1) genetic polymorphisms on acute and chronic pain after intrathecal morphine for caesarean section: a prospective cohort study. , 2010, International journal of obstetric anesthesia.

[90]  W. Maixner,et al.  Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study , 2010, Pharmacogenetics and genomics.

[91]  J. Ott,et al.  ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. , 2008, Human molecular genetics.

[92]  D. Campa,et al.  Association of ABCB1/MDR1 and OPRM1 Gene Polymorphisms With Morphine Pain Relief , 2008, Clinical pharmacology and therapeutics.

[93]  R. Fainsinger,et al.  A “TNM” classification system for cancer pain: The Edmonton Classification System for Cancer Pain (ECS-CP) , 2008, Supportive Care in Cancer.

[94]  S. Kaasa,et al.  Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain , 2008, Molecular pain.

[95]  F. Musshoff,et al.  Determination of Opioid Analgesics in Hair Samples Using Liquid Chromatography/Tandem Mass Spectrometry and Application to Patients Under Palliative Care , 2007, Therapeutic drug monitoring.

[96]  Raymond A. Dionne,et al.  Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs , 2006 .

[97]  R. Fainsinger,et al.  A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain , 2005, Palliative medicine.

[98]  A. Vigano,et al.  A multicenter study of the revised Edmonton Staging System for classifying cancer pain in advanced cancer patients. , 2005, Journal of pain and symptom management.

[99]  D. Carr,et al.  Agreement between percentage pain reductions calculated from numeric rating scores of pain intensity and those reported by patients with acute or cancer pain , 2003, Pain.

[100]  S. Ward,et al.  Patient satisfaction and pain severity as outcomes in pain management: a longitudinal view of one setting's experience. , 1996, Journal of pain and symptom management.

[101]  E. Bruera,et al.  A prospective multicenter assessment of the Edmonton staging system for cancer pain. , 1995, Journal of pain and symptom management.

[102]  Eduardo Bruera,et al.  The Edmonton Symptom Assessment System (ESAS): A Simple Method for the Assessment of Palliative Care Patients , 1991, Journal of palliative care.

[103]  E. Bruera,et al.  The Edmonton staging system for cancer pain: preliminary report , 1989, Pain.

[104]  J. Mao,et al.  Genetic Predictors of Response to Acupuncture for Aromatase Inhibitor–Associated Arthralgia Among Breast Cancer Survivors , 2019, Pain medicine.

[105]  M. Hjermstad,et al.  Development of an item bank for computerized adaptive test (CAT) measurement of pain , 2015, Quality of Life Research.

[106]  A. Sharara,et al.  Radiation Enteritis , 2014, Current Gastroenterology Reports.

[107]  A. Melemeni,et al.  Acute postoperative pain predicts chronic pain and long-term analgesic requirements after breast surgery for cancer. , 2008, Acta anaesthesiologica Belgica.

[108]  A. Comley,et al.  Assessing patient satisfaction with pain management through a continuous quality improvement effort. , 2001, Journal of pain and symptom management.