{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:35:53Z","timestamp":1791516953060,"version":"4.3.4"},"reference-count":88,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is a hematological malignancy with a poor prognosis while with a long and progressive outcome. To date, the therapeutic options are restricted to few drugs, including thalidomide or its derivates and autologous transplantation including stem-cell transplantation. More recently, the use of both proteasome inhibitors and monoclonal antibodies have been included in MM therapy, but the clinical results are still under evaluation. Unfortunately, death rates (within the 5-year overall survival rates) are still very high (45%), with no relevant improvement over the past 10 years. Here, we discuss data supporting a new therapeutic approach against MM, based on a common phenotype of tumor malignancies, which is the acidic microenvironment. Extracellular acidity drastically reduces the efficacy of both anti-tumor drugs and the immune reaction against tumors. Pre-clinical data have shown that anti-acidic drugs, such as proton pump inhibitors (PPIs), have a potent cytotoxic effect against human MM cells, thus supporting their use in the treatment of this malignancy. Here, we discuss also similarities between MM and type II diabetes mellitus (DM) with high risk of developing MM, suggesting that both anti-diabetic drugs and a hypocaloric diet may help in curing MM patients.<\/jats:p>","DOI":"10.3390\/cancers12113226","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T09:04:46Z","timestamp":1604307886000},"page":"3226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Acidic Microenvironment: Is It a Phenotype of All Cancers? A Focus on Multiple Myeloma and Some Analogies with Diabetes Mellitus"],"prefix":"10.3390","volume":"12","author":[{"given":"Stefano","family":"Fais","sequence":"first","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0 (National Institute of Health), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-0937","authenticated-orcid":false,"given":"Yoshinori","family":"Marunaka","sequence":"additional","affiliation":[{"name":"Research Institute for Clinical Physiology, Kyoto Industrial Health Association, Kyoto 604-8472, Japan"},{"name":"Research Center for Drug Discovery and Pharmaceutical Development Science, Research Organization of Science and Technology, Ritsumeikan University, Kusatsu 525-8577, Japan"},{"name":"Department of Molecular Cell Physiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0609.2010.01542.x","article-title":"Emerging therapies for the treatment of relapsed or refractory multiple myeloma","volume":"86","author":"Dimopoulos","year":"2011","journal-title":"Eur. 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