Journal of Clinical Trials, Pathology and Case Studies
Molecular Profiling of an Exceptional Responder and a Non-Responder to Platinum Based Chemotherapy in Two Patients with Advanced Urothelial Cancer
- 1Department of Internal Medicine, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona
- 2Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, Arizona
- 3The University of Arizona Cancer Center at St. Joseph’s Hospital and Medical Center, Phoenix, Arizona
Jue Wang, The University of Arizona Cancer Center at St. Joseph’s Hospital and Medical Center, 625 N 6th Street, Phoenix, AZ 85004, Tel: 1-602-406-8222; E-mail: email@example.com
Wang, T., et al. Molecular Profiling of an Exceptional Responder and a Non-Responder to Platinum Based Chemotherapy in Two Patients with Advanced Urothelial Cancer. (2016) Clin Trials Case Stud 1(1): 35- 38.
© 2016 Wang, J. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
KeywordsMolecular profiling; Gemcitabine; Cisplatin; Urothelial cancer;
Background: Understanding the molecular mechanisms of sensitivity to anticancer therapies may improve patient selection, response to therapy, and clinical trial designs. One approach to increase this understanding involves detailed studies of exceptional responders who achieved exquisite sensitivity or durable responses to therapy, and non- responders who have intrinsic or acquired drug resistance to therapy.
Case presentation: Case 1: A 72-year-old man developed multiple lung metastases three years after initial diagnosis of low-grade urothelial carcinoma followed with left nephroureterectomy and multiple courses of intra-vesical BCG therapy. He was enrolled into a randomized, phase III study of gemcitabine/cisplatin plus/minus bevacizumab therapy. He had a near complete response after two cycles of chemotherapy. The samples from his primary tumor and metastatic lesions were examined with a battery of immunohistochemical and molecular assays.
Case 2: A 41-year-old female with history of pT3bpN2, high-grade transitional cell carcinoma of the bladder, status post radical cystectomy received four cycles of adjuvant gemcitabine/cisplatin. Three months afterwards, she was found with large pelvic metastases. The samples from her pelvic mass were examined with immunohistochemical and molecular assays.
Conclusion: Case 1 patient has low expression of ERCC1 and RRM1 and mutations of BRCA1 and ATM. Case 2 patient has amplification of AKT1. The molecular profiling of two cases provides potential explanation for the exceptional response and non-response to gemcitabine/cisplatin respectively. Other actionable gene alterations provide rational basis for future targets. An in-depth analysis of tumor molecular profile will facilitate new drug development and provide new insights into urothelial carcinoma.