title: Therapeutic approach guided by genetic alteration: use of MTOR inhibitor in renal medullary carcinoma with loss of PTEN expression.
abstract: Renal Medullary Cancer (RMC) is a rare and aggressive type of renal cell cancer that presents predominantly in patients with sickle cell hemoglobinopathies, and is typically metastatic at the time of presentation. Although platinum based chemotherapeutic regimens have recently emerged as the best option for producing a clinically significant response as reported in various case series, the response is far from satisfactory, as most RMC patients still succumb to their disease within a year of diagnosis. There is currently no standard of care for treatment of this disease. We report, to our knowledge, the first case of RMC where in molecular characterization of the tumor was used to guide therapy. In our patient, molecular analysis identified a decreased expression of Ribonucleotide Reductase M1(RRM1) and phosphatase and tensin homolog (PTEN). Based on these results of PTEN deficiency, we started our patient on everolimus (an MTOR inhibitor) maintenance after treating him with an induction chemotherapy regimen of Paclitaxel-Cisplatin-Gemcitabine (PCG). His tumor responded to induction therapy and he went into complete remission and remained in remission for 7 months. He is now alive about 14 months from his diagnosis and is asymptomatic with minimal disease. The rarity of RMC makes it very difficult to do any meaningful clinical trials in this group of patients. The overall prognosis for RMC remains very poor and knowledge about driver mutations may help in guiding therapy to improve survival in this select group of patients, where there is dearth of available therapies.
authors.affiliation: a Penn State College of Medicine Hershey , PA USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Lipkin
authors.forename: Syed M
authors.initials: SM
authors.lastname: Rizvi
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Nabeel E
authors.initials: NE
authors.lastname: Sarwani
authors.forename: Sheldon L
authors.initials: SL
authors.lastname: Holder
authors.forename: Mathew
authors.initials: M
authors.lastname: Kaag
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Drabick
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001706:Biopsy; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012262:Ribonucleoside Diphosphate Reductase; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase
keywords: MTOR; PTEN; RRM1; cisplatin; everolimus; maintenance-therapy; renal medullary carcinoma