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dc.contributor.authorMahmood, J.
dc.contributor.authorShukla, H.D.
dc.contributor.authorSoman, S.
dc.date.accessioned2019-06-05T18:28:13Z
dc.date.available2019-06-05T18:28:13Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85058495868&doi=10.3390%2fcancers10120469&partnerID=40&md5=58417444a3fafca6c8b08d7b66dcdb5f
dc.identifier.urihttp://hdl.handle.net/10713/9397
dc.description.abstractPancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42–43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients. Copyright 2018 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorshipSeed grant from Department of Radiation Oncology, University of Maryland, Baltimore, School of Medicine and a partial grant from the William & Ella Owens Medical Research Foundation.en_US
dc.description.urihttps://dx.doi.org/10.3390/cancers10120469en_US
dc.language.isoen-USen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancers
dc.subjectImmunotherapyen_US
dc.subjectMetastasisen_US
dc.subjectPancreatic canceren_US
dc.subjectRadiation therapyen_US
dc.subjectTargeted hyperthermiaen_US
dc.subjectTripartiteen_US
dc.subjectTumor microenvironmenten_US
dc.titleImmunotherapy, radiotherapy, and hyperthermia: A combined therapeutic approach in pancreatic cancer treatmenten_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers10120469


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