{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:27:37Z","timestamp":1793834857206,"version":"4.6.1"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyretin (ATTR) or light chain (AL) amyloidosis. ATTR CA may result from a genetic mutation in the <jats:italic>TTR<\/jats:italic> gene, which is inherited (ATTRv), or from age-related deposition from wild-type ATTR (ATTRwt). Cardiac involvement in AL amyloidosis is attributed to either of two mechanisms: the extracellular deposition of amyloid fibril in the myocardium, or direct cardiotoxicity from the fibril aggregates. Typing of amyloid fibrils, a critical determinant of therapy, has also improved with wider availability of laser capture and mass spectrometry of histologic specimens. Specific and accurate evaluation of CA is now possible using cardiac magnetic resonance imaging and bone scintigraphy tracers. Survival in CA has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilizers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise and may improve outcomes in systemic and cardiac amyloidoses. Treatment strategies for CA has recently undergone transformative changes, leading to some progress in outcomes for certain patients. Here, we discuss the basic features of CA as well as the emergence of novel, disease-modifying strategies that have been recently evaluated in clinical trials for the treatment of CA.<\/jats:p>","DOI":"10.3389\/fmed.2024.1477988","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T04:29:06Z","timestamp":1730262546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["A review of recent clinical trials to evaluate disease-modifying therapies in the treatment of cardiac amyloidosis"],"prefix":"10.3389","volume":"11","author":[{"given":"Sindhuja","family":"Senigarapu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Driscoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"B1","article-title":"Systemic immunoglobulin light chain amyloidosis.","volume":"4","author":"Merlini","year":"2018","journal-title":"Nat Rev Dis Prim."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000454","article-title":"Systemic AL amyloidosis: Current approaches to diagnosis and management.","volume":"4","author":"Fotiou","year":"2020","journal-title":"Hemasphere."},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-021-00486-4","article-title":"Comprehensive review of AL amyloidosis: Some practical recommendations.","volume":"11","author":"Al Hamed","year":"2021","journal-title":"Blood Cancer J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.6004\/jnccn.2023.0001","article-title":"Systemic light chain amyloidosis, version 2.2023, NCCN clinical practice guidelines in oncology.","volume":"21","author":"Kumar","year":"2023","journal-title":"J Natl Compr Cancer Netw."},{"key":"B5","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1200\/OP.22.00396","article-title":"Diagnostic and treatment strategies for AL amyloidosis in an era of therapeutic innovation.","volume":"19","author":"Dima","year":"2023","journal-title":"JCO Oncol Pract."},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1039\/C9CS00199A","article-title":"Half a century of amyloids: Past, present and future.","volume":"49","author":"Ke","year":"2020","journal-title":"Chem Soc Rev."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13169","article-title":"Systemic amyloidosis from A (AA) to T (ATTR): A review.","volume":"289","author":"Muchtar","year":"2021","journal-title":"J Intern Med."},{"key":"B8","author":"Gorevic","year":"2024","journal-title":"Overview of Amyloidosis, Uptodate"},{"key":"B9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nrm3810","article-title":"The amyloid state and its association with protein misfolding diseases.","volume":"15","author":"Knowles","year":"2014","journal-title":"Nat Rev Mol Cell Biol."},{"key":"B10","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1016\/j.jacc.2019.04.003","article-title":"Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review.","volume":"73","author":"Ruberg","year":"2019","journal-title":"J Am Coll Cardiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","article-title":"Hereditary transthyretin amyloidosis: A model of medical progress for a fatal disease.","volume":"15","author":"Adams","year":"2019","journal-title":"Nat Rev Neurol."},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-022-02414-6","article-title":"Global epidemiology of amyloid light-chain amyloidosis.","volume":"17","author":"Kumar","year":"2022","journal-title":"Orphanet J Rare Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1001\/jama.2020.5493","article-title":"Systemic amyloidosis recognition, prognosis, and therapy: A systematic review.","volume":"324","author":"Gertz","year":"2020","journal-title":"JAMA."},{"key":"B14","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.jaccao.2021.09.003","article-title":"AL amyloidosis: Current chemotherapy and immune therapy treatment strategies: JACC: CardioOncology state-of-the-art review.","volume":"3","author":"Bianchi","year":"2021","journal-title":"JACC CardioOncol."},{"key":"B15","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.hoc.2020.08.001","article-title":"Systemic amyloidosis due to clonal plasma cell diseases.","volume":"34","author":"Bianchi","year":"2020","journal-title":"Hematol Oncol Clin North Am."},{"key":"B16","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1001\/jama.2024.0442","article-title":"Cardiac amyloidosis due to transthyretin protein: A review.","volume":"331","author":"Ruberg","year":"2024","journal-title":"JAMA."},{"key":"B17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.14797\/mdcvj.1070","article-title":"Light chain amyloidosis: Epidemiology, staging, and prognostication.","volume":"18","author":"Baker","year":"2022","journal-title":"Methodist Debakey Cardiovasc J."},{"key":"B18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1182\/blood-2016-01-629790","article-title":"What is new in diagnosis and management of light chain amyloidosis.","volume":"128","author":"Palladini","year":"2016","journal-title":"Blood."},{"key":"B19","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41375-020-0800-6","article-title":"Immunogenetic characterization of clonal plasma cells in systemic light-chain amyloidosis.","volume":"35","author":"Cuenca","year":"2021","journal-title":"Leukemia."},{"key":"B20","first-page":"813","article-title":"AL amyloidosis: Unfolding a complex disease.","volume":"10","author":"Lu","year":"2019","journal-title":"J Adv Pract Oncol."},{"key":"B21","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nrneph.2013.171","article-title":"Pathophysiology and treatment of systemic amyloidosis.","volume":"9","author":"Gillmore","year":"2013","journal-title":"Nat Rev Nephrol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/bjh.13805","article-title":"Recent advances in the management of AL Amyloidosis.","volume":"172","author":"Kastritis","year":"2016","journal-title":"Br J Haematol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.3324\/haematol","article-title":"Light chain amyloidosis associated with Waldenstr\u00f6m macroglobulinemia: Treatment and survival outcomes.","volume":"108","author":"Gustine","year":"2023","journal-title":"Haematologica."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4319","DOI":"10.1200\/JCO.2013.50.8499","article-title":"Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis.","volume":"31","author":"Kourelis","year":"2013","journal-title":"J Clin Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"232","DOI":"10.4065\/mcp.2009.0547","article-title":"Clinical features and treatment response of light chain (AL) amyloidosis diagnosed in patients with previous diagnosis of multiple myeloma.","volume":"85","author":"Madan","year":"2010","journal-title":"Mayo Clin Proc."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3517","DOI":"10.1093\/cvr\/cvac119","article-title":"Transthyretin cardiac amyloidosis.","volume":"118","author":"Porcari","year":"2023","journal-title":"Cardiovasc Res."},{"key":"B27","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000506696","article-title":"The pathology of amyloidosis in classification: A review.","volume":"143","author":"Picken","year":"2020","journal-title":"Acta Haematol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1080\/13506129.2020.1835263","article-title":"Amyloid nomenclature 2020: Update and recommendations by the international society of amyloidosis (ISA) nomenclature committee.","volume":"27","author":"Benson","year":"2020","journal-title":"Amyloid."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.jacc.2022.11.0227","article-title":"2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis: A report of the American College of Cardiology Solution Set Oversight Committee.","volume":"81","author":"Writing Committee, Kittleson","year":"2023","journal-title":"J Am Coll Cardiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1007\/s00018-009-0109-0","article-title":"Transthyretin: The servant of many masters.","volume":"66","author":"Buxbaum","year":"2009","journal-title":"Cell Mol Life Sci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1080\/13506129.2022.2147636","article-title":"Amyloid nomenclature 2022: Update, novel proteins, and recommendations by the international society of amyloidosis (ISA) nomenclature committee.","volume":"29","author":"Buxbaum","year":"2022","journal-title":"Amyloid."},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10081906","article-title":"The journey of human transthyretin: Synthesis, structure stability, and catabolism.","volume":"10","author":"Sanguinetti","year":"2022","journal-title":"Biomedicines."},{"key":"B33","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1177\/0300060518814337","article-title":"Multiorgan involvement by amyloid light chain amyloidosis.","volume":"47","author":"Li","year":"2019","journal-title":"J Int Med Res."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2023.1242815","article-title":"Hereditary transthyretin amyloidosis: A comprehensive review with a focus on peripheral neuropathy.","volume":"14","author":"Poli","year":"2023","journal-title":"Front Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3538","DOI":"10.1111\/jgs.17976","article-title":"Analysis of lumbar spine stenosis specimens for identification of amyloid.","volume":"70","author":"Maurer","year":"2022","journal-title":"J Am Geriatr Soc."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1016\/j.jacc.2018.07.092","article-title":"Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release.","volume":"72","author":"Sperry","year":"2018","journal-title":"J Am Coll Cardiol."},{"key":"B37","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.111.000364","article-title":"Updates in cardiac amyloidosis: A review.","volume":"1","author":"Banypersad","year":"2012","journal-title":"J Am Heart Assoc."},{"key":"B38","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2147\/IJNRD.S84784","article-title":"Dialysis-related amyloidosis: Challenges and solutions.","volume":"9","author":"Scarpioni","year":"2016","journal-title":"Int J Nephrol Renovasc Dis."},{"key":"B39","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.tcm.2017.07.004","article-title":"Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment.","volume":"28","author":"Siddiqi","year":"2018","journal-title":"Trends Cardiovasc Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.jaccao.2021.06.006","article-title":"ATTR amyloidosis: Current and emerging management strategies: JACC: CardioOncology state-of-the-art review.","volume":"3","author":"Griffin","year":"2021","journal-title":"J Am Coll Cardiol CardioOncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2147\/TCRM.S219979","article-title":"Diagnosis and treatment of hereditary transthyretin amyloidosis (hATTR) polyneuropathy: Current perspectives on improving patient care.","volume":"16","author":"Luigetti","year":"2020","journal-title":"Ther Clin Risk Manag."},{"key":"B42","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/mus.20821","article-title":"The molecular biology and clinical features of amyloid neuropathy.","volume":"36","author":"Benson","year":"2007","journal-title":"Muscle Nerve."},{"key":"B43","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.130285.1","article-title":"A review of recent advances in the diagnosis of cardiac amyloidosis, treatment of its cardiac complications, and disease-modifying therapies.","volume":"12","author":"Raval","year":"2023","journal-title":"F1000Res."},{"key":"B44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/13506129.2020.1764928","article-title":"DISCOVERY: Prevalence of transthyretin (TTR) mutations in a US-centric patient population suspected of having cardiac amyloidosis.","volume":"27","author":"Akinboboye","year":"2020","journal-title":"Amyloid."},{"key":"B45","article-title":"Amyloidosis and glomerular diseases in familial mediterranean fever.","volume":"57","author":"Siligato","year":"2021","journal-title":"Medicina (Kaunas)."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1007\/s40120-022-00385-1","article-title":"Three newly recognized likely pathogenic gene variants associated with hereditary transthyretin amyloidosis.","volume":"11","author":"Patel","year":"2022","journal-title":"Neurol Ther."},{"key":"B47","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1056\/NEJMoa013354","article-title":"Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.","volume":"346","author":"Lachmann","year":"2002","journal-title":"N Engl J Med."},{"key":"B48","article-title":"Hereditary transthyretin amyloidosis.","author":"Sekijima","year":"2001","journal-title":"GeneReviews\u00a7"},{"key":"B49","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s10072-020-04889-2","article-title":"Hereditary transthyretin amyloidosis overview.","volume":"43","author":"Manganelli","year":"2020","journal-title":"Neurol Sci."},{"key":"B50","article-title":"Amyloidosis of the heart: A comprehensive review.","volume":"15","author":"Imdad","year":"2023","journal-title":"Cureus."},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.113.000098","article-title":"Senile systemic amyloidosis: Clinical features at presentation and outcome.","volume":"2","author":"Pinney","year":"2013","journal-title":"J Am Heart Assoc."},{"key":"B52","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1080\/07853890701842988","article-title":"Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: A population-based autopsy study.","volume":"40","author":"Tanskanen","year":"2008","journal-title":"Ann Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1080\/13506129.2022.2128331","article-title":"Distribution and progression of cerebral amyloid angiopathy in early-onset V30M (p.V50M) hereditary ATTR amyloidosis.","volume":"30","author":"Takahashi","year":"2023","journal-title":"Amyloid."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10102394","article-title":"Hereditary transthyretin-related amyloidosis: Genetic heterogeneity and early personalized gene therapy.","volume":"10","author":"Dugo","year":"2022","journal-title":"Biomedicines."},{"key":"B55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/asheducation-2017.1.1","article-title":"AL amyloidosis: From molecular mechanisms to targeted therapies.","volume":"2017","author":"Merlini","year":"2017","journal-title":"Hematol Am Soc Hematol Educ Program Book."},{"key":"B56","doi-asserted-by":"publisher","first-page":"72","DOI":"10.2174\/011573403X240302230925043500","article-title":"Cardiac amyloidosis: A contemporary review of medical and surgical therapy.","volume":"20","author":"Brownell","year":"2024","journal-title":"Curr Cardiol Rev."},{"key":"B57","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1093\/eurheartj\/ehab072","article-title":"Diagnosis and treatment of cardiac amyloidosis: A position statement of the ESC working group on myocardial and pericardial diseases.","volume":"42","author":"Garcia-Pavia","year":"2021","journal-title":"Eur Heart J."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1007\/s11684-017-0516-9","article-title":"Transthyretin (TTR) cardiac amyloidosis.","volume":"26","author":"Ruberg","year":"2012","journal-title":"Circulation."},{"key":"B59","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/gim.2016.200","article-title":"Transthyretin V122I (pV142I)* cardiac amyloidosis: An age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans.","volume":"19","author":"Buxbaum","year":"2017","journal-title":"Genet Med."},{"key":"B60","doi-asserted-by":"crossref","first-page":"s30","DOI":"10.7861\/clinmedicine.18-2-s30","article-title":"Cardiac amyloidosis.","volume":"18","author":"Martinez-Naharro","year":"2018","journal-title":"Clin Med (Lond)."},{"key":"B61","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1161\/CIR.0000000000000792","article-title":"American heart association heart failure and transplantation committee of the council on clinical cardiology. cardiac amyloidosis: Evolving diagnosis and management: A scientific statement from the American heart association.","volume":"142","author":"Kittleson","year":"2020","journal-title":"Circulation."},{"key":"B62","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.jaccao.2021.05.004","article-title":"Two decades of cardiac amyloidosis: A Danish nationwide study.","volume":"3","author":"Westin","year":"2021","journal-title":"JACC CardioOncol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/13506129.2018.1556156","article-title":"Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations.","volume":"26","author":"Concei\u00e7\u00e3o","year":"2019","journal-title":"Amyloid."},{"key":"B64","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1161\/CIRCULATIONAHA.116.021612","article-title":"Nonbiopsy diagnosis of cardiac transthyretin amyloidosis.","volume":"133","author":"Gillmore","year":"2016","journal-title":"Circulation."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2020.100720","article-title":"The diagnostic challenges of cardiac amyloidosis: A practical approach to the two main types.","volume":"45","author":"Varga","year":"2021","journal-title":"Blood Rev."},{"key":"B66","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1056\/NEJMoa1716793","article-title":"Inotersen treatment for patients with hereditary transthyretin amyloidosis.","volume":"379","author":"Benson","year":"2018","journal-title":"N Engl J Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1161\/CIRCULATIONAHA.116.024438","article-title":"Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis.","volume":"135","author":"Maurer","year":"2017","journal-title":"Circulation."},{"key":"B68","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/HCO.0000000000000841","article-title":"Clinical approach to genetic testing in amyloid cardiomyopathy: From mechanism to effective therapies.","volume":"36","author":"Alreshq","year":"2021","journal-title":"Curr Opin Cardiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1002\/ehf2.14337","article-title":"FINC-94 Network. Patients with cardiac amyloidosis are at a greater risk of mortality and hospital readmission after acute heart failure.","volume":"10","author":"Berthelot","year":"2023","journal-title":"ESC Heart Fail."},{"key":"B70","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-44912-x","article-title":"Predictors of mortality in light chain cardiac amyloidosis with heart failure.","volume":"9","author":"Tahir","year":"2019","journal-title":"Sci Rep."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.005407","article-title":"Epidemiology of cardiac amyloidosis-associated heart failure hospitalizations among fee-for-service medicare beneficiaries in the United States.","volume":"12","author":"Gilstrap","year":"2019","journal-title":"Circ Heart Fail."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/13506129.2022.2093635","article-title":"Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group.","volume":"30","author":"Wechalekar","year":"2023","journal-title":"Amyloid."},{"key":"B73","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1365-2559.2007.02658.x","article-title":"Bone marrow findings correlate with clinical outcome in systemic AL amyloidosis patients.","volume":"50","author":"Hasserjian","year":"2007","journal-title":"Histopathology."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejim.2019.07.022","article-title":"Cardiac amyloidosis: An underdiagnosed\/underappreciated disease.","volume":"67","author":"Manolis","year":"2019","journal-title":"Eur J Intern Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1182\/blood-2002-06-1698","article-title":"Circulating peripheral blood plasma cells as a prognostic indicator in patients with primary systemic amyloidosis.","volume":"101","author":"Pardanani","year":"2003","journal-title":"Blood."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1182\/blood-2015-08-662726","article-title":"Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience.","volume":"126","author":"Sanchorawala","year":"2015","journal-title":"Blood."},{"key":"B77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13506129.2021.2002841","article-title":"Guidelines for high dose chemotherapy and stem cell transplantation for systemic AL amyloidosis: EHA-ISA working group guidelines.","volume":"29","author":"Sanchorawala","year":"2022","journal-title":"Amyloid."},{"key":"B78","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1182\/blood-2006-03-001164","article-title":"Dangerous small B-cell clones.","volume":"108","author":"Merlini","year":"2006","journal-title":"Blood."},{"key":"B79","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1182\/blood.2019000834","article-title":"A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib.","volume":"134","author":"Manwani","year":"2019","journal-title":"Blood."},{"key":"B80","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41418-020-00703-w","article-title":"The ubiquitin system: From cell signalling to disease biology and new therapeutic opportunities.","volume":"28","author":"Damgaard","year":"2021","journal-title":"Cell Death Differ."},{"key":"B81","first-page":"197","article-title":"The role of the proteasome in cellular protein degradation.","volume":"9","author":"Driscoll","year":"1994","journal-title":"Histol Histopathol."},{"key":"B82","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1053\/j.seminhematol.2012.04.002","article-title":"Targeting the ubiquitin+proteasome system in solid tumors.","volume":"49","author":"Driscoll","year":"2012","journal-title":"Semin Hematol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1073\/pnas.86.3.787","article-title":"Skeletal muscle proteasome can degrade proteins in an ATP-dependent process that does not require ubiquitin.","volume":"86","author":"Driscoll","year":"1989","journal-title":"Proc Natl Acad Sci USA."},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.925804","article-title":"Targeting proteasomes in cancer and infectious disease: A parallel strategy to treat malignancies and microbes.","volume":"12","author":"Ignatz-Hoover","year":"2022","journal-title":"Front Cell Infect Microbiol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.canlet.2012.06.016","article-title":"Molecular crosstalk between the proteasome, aggresomes and autophagy: Translational potential and clinical implications.","volume":"325","author":"Driscoll","year":"2012","journal-title":"Cancer Lett."},{"key":"B86","doi-asserted-by":"crossref","first-page":"647","DOI":"10.20517\/cdr.2022.23","article-title":"Therapeutics to harness the immune microenvironment in multiple myeloma.","volume":"5","author":"Ignatz-Hoover","year":"2022","journal-title":"Cancer Drug Resist."},{"key":"B87","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.1016\/S0021-9258(19)34041-4","article-title":"The proteasome (multicatalytic protease) is a component of the 1500-kDa proteolytic complex which degrades ubiquitin-conjugated proteins.","volume":"265","author":"Driscoll","year":"1990","journal-title":"J Biol Chem."},{"key":"B88","doi-asserted-by":"publisher","first-page":"4986","DOI":"10.1073\/pnas.89.11.4986","article-title":"An ATP-stabilized inhibitor of the proteasome is a component of the 1500-kDa ubiquitin conjugate-degrading complex.","volume":"89","author":"Driscoll","year":"1992","journal-title":"Proc Natl Acad Sci USA."},{"key":"B89","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev-biochem-062917-011931","article-title":"Structure and function of the 26S proteasome.","volume":"87","author":"Bard","year":"2018","journal-title":"Annu Rev Biochem."},{"key":"B90","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1515\/hsz-2011-0285","article-title":"The proteasome: Molecular machinery and pathophysiological roles.","volume":"393","author":"Tanaka","year":"2012","journal-title":"Biol Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10555-017-9698-5","article-title":"Emerging small molecule approaches to enhance the antimyeloma benefit of proteasome inhibitors.","volume":"36","author":"Driscoll","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"B92","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1073\/pnas.86.8.2597","article-title":"Involvement of the proteasome in various degradative processes in mammalian cells.","volume":"86","author":"Matthews","year":"1989","journal-title":"Proc Natl Acad Sci USA."},{"key":"B93","first-page":"166","article-title":"Emerging strategies to manage relapsed and\/or refractory multiple myeloma.","volume":"37","author":"Driscoll","year":"2023","journal-title":"Oncology."},{"key":"B94","doi-asserted-by":"publisher","first-page":"4867","DOI":"10.1200\/JCO.2006.07.9665","article-title":"Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma.","volume":"24","author":"Fisher","year":"2006","journal-title":"J Clin Oncol."},{"key":"B95","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1038\/bmt.2013.98","article-title":"Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: Analysis of SWOG trial S0115.","volume":"48","author":"Sanchorawala","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"B96","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, bortezomib, and dexamethasone for multiple myeloma.","volume":"375","author":"Palumbo","year":"2016","journal-title":"N Engl J Med."},{"key":"B97","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1189\/jlb.1011497","article-title":"Pivotal advance: Protein synthesis modulates responsiveness of differentiating and malignant plasma cells to proteasome inhibitors.","volume":"92","author":"Cenci","year":"2012","journal-title":"J Leukoc Biol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1182\/blood-2011-11-390930","article-title":"Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis.","volume":"119","author":"Mikhael","year":"2012","journal-title":"Blood."},{"key":"B99","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1200\/JCO.2009.23.8220","article-title":"Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis.","volume":"28","author":"Kastritis","year":"2010","journal-title":"J Clin Oncol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1182\/blood-2015-01-620302","article-title":"A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis.","volume":"126","author":"Palladini","year":"2015","journal-title":"Blood."},{"key":"B101","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1200\/JCO.20.01285","article-title":"Bortezomib, melphalan, and dexamethasone for light-chain amyloidosis.","volume":"38","author":"Kastritis","year":"2020","journal-title":"J Clin Oncol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.3324\/haematol.2014.104109","article-title":"Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-na\u00efve patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III).","volume":"99","author":"Jaccard","year":"2014","journal-title":"Haematologica."},{"key":"B103","doi-asserted-by":"publisher","first-page":"3040","DOI":"10.1182\/blood-2008-08-172734","article-title":"The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition.","volume":"113","author":"Bianchi","year":"2009","journal-title":"Blood."},{"key":"B104","doi-asserted-by":"publisher","first-page":"517","DOI":"10.2174\/1568009614666140804154511","article-title":"Overview of proteasome inhibitor-based anti-cancer therapies: Perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system.","volume":"14","author":"Dou","year":"2014","journal-title":"Curr Cancer Drug Targets."},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1141851","article-title":"Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.","volume":"13","author":"Rana","year":"2023","journal-title":"Front Oncol."},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01234-2","article-title":"Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma.","volume":"15","author":"Swamydas","year":"2022","journal-title":"J Hematol Oncol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1158\/2767-9764.CRC-23-0528","article-title":"HDAC6 inhibition releases HR23B to activate proteasomes, expand the tumor immunopeptidome and amplify T-cell antimyeloma activity.","volume":"4","author":"Rana","year":"2024","journal-title":"Cancer Res Commun."},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.957157","article-title":"Road testing new CAR design strategies in multiple myeloma.","volume":"13","author":"Rana","year":"2022","journal-title":"Front Immunol."},{"key":"B109","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-021-01053-x","article-title":"Novel therapies emerging in oncology to target the TGF\u03b2 pathway.","volume":"14","author":"Kim","year":"2021","journal-title":"J Hematol Oncol."},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-23-0931","article-title":"Immunoproteasome activation expands the MHC-class I immunopeptidome, unmasks neoantigens and enhances T-cell anti-myeloma activity.","author":"Rana","year":"2024","journal-title":"Mol Cancer Ther"},{"key":"B111","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1056\/NEJMoa2028631","article-title":"Daratumumab-based treatment for immunoglobulin light-chain amyloidosis.","volume":"385","author":"Kastritis","year":"2021","journal-title":"N Engl J Med."},{"key":"B112","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1111\/bjh.18733","article-title":"First report of outcomes in patients with stage IIIb AL amyloidosis treated with Dara-VCD front-line therapy.","volume":"201","author":"Chakraborty","year":"2023","journal-title":"Br J Haematol."},{"key":"B113","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","article-title":"Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.","volume":"379","author":"Maurer","year":"2018","journal-title":"N Engl J Med."},{"key":"B114","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1056\/NEJMoa2305434","article-title":"Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy.","volume":"390","author":"Gillmore","year":"2024","journal-title":"N Engl J Med."},{"key":"B115","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1056\/NEJMoa2300757","article-title":"Patisiran treatment in patients with transthyretin cardiac amyloidosis.","volume":"389","author":"Maurer","year":"2023","journal-title":"N Engl J Med."},{"key":"B116","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1056\/NEJMra023144","article-title":"Molecular mechanisms of amyloidosis.","volume":"349","author":"Merlini","year":"2003","journal-title":"N Engl J Med."},{"key":"B117","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1056\/NEJMe2309308","article-title":"A step forward in solving amyloidosis.","volume":"389","author":"Merlini","year":"2023","journal-title":"N Engl J Med."},{"key":"B118","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1056\/NEJMe1805499","article-title":"Oligonucleotide drugs for transthyretin amyloidosis.","volume":"379","author":"Buxbaum","year":"2018","journal-title":"N Engl J Med."},{"key":"B119","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1056\/NEJMoa2303765","article-title":"Phase 1 trial of antibody NI006 for depletion of cardiac transthyretin amyloid.","volume":"389","author":"Garcia-Pavia","year":"2023","journal-title":"N Engl J Med."},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2409134","article-title":"Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy.","author":"Fontana","year":"2024","journal-title":"N Engl J Med"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3390\/life13071518","article-title":"AL amyloidosis and multiple myeloma: A complex scenario in which cardiac involvement remains the key prognostic factor.","volume":"13","author":"R\u00ed,os-Tamayo","year":"2023","journal-title":"Life (Basel)."},{"key":"B122","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1182\/blood.2020006913","article-title":"Management of AL amyloidosis in 2020.","volume":"136","author":"Palladini","year":"2020","journal-title":"Blood."},{"key":"B123","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1080\/13506129.2022.2052838","article-title":"Guidelines and new directions in the therapy and monitoring of ATTRv amyloidosis.","volume":"29","author":"Ando","year":"2022","journal-title":"Amyloid."},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114129","article-title":"CD38 and anti-CD38 monoclonal antibodies in AL amyloidosis: Targeting plasma cells and beyond.","volume":"21","author":"Roccatello","year":"2020","journal-title":"Int J Mol Sci."},{"key":"B125","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s10557-019-06919-4","article-title":"Phase 3 multicenter study of revusiran in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with cardiomyopathy (ENDEAVOUR).","volume":"34","author":"Judge","year":"2020","journal-title":"Cardiovasc Drugs Ther."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1477988\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T04:29:22Z","timestamp":1730262562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1477988\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":125,"alternative-id":["10.3389\/fmed.2024.1477988"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1477988","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"article-number":"1477988"}}