Comparison of clinical staging of benign and malignant ovarian tissues with DNA flow cytometry

Thornthwaite, Jerry T.; Stanfill, J. Clint; Ahmed, Ahmed

doi:10.5430/jst.v3n5p12

Cited by 1 publication

(1 citation statement)

References 60 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study we took advantage of large collection of serous OC biospecimens and ovarian PDXs at Mayo Clinic by profiling ovarian tumors for genomic alterations and examining responses to targeted therapy selected based on genomic findings in PDXs. HGS‐OC are known to have a high genomic instability (Malek et al ., ; McBride et al ., ; Patch et al ., ) as well as aneuploidy (Silvestrini et al ., ; Thornthwaite et al ., ). Thus, in our study we focused on analyses of structural genomic alterations and CNVs (Harris et al ., ) to identify potentially targetable changes using the MP sequencing protocol.…”

Section: Discussionmentioning

confidence: 97%

Targeting HER2 in patient‐derived xenograft ovarian cancer models sensitizes tumors to chemotherapy

et al. 2018

View full text Add to dashboard Cite

Ovarian cancer is the most lethal gynecologic malignancy. About 75% of ovarian cancer patients relapse and/or develop chemo‐resistant disease after initial response to standard‐of‐care treatment with platinum‐based therapies. HER2 amplifications and overexpression in ovarian cancer are reported to vary, and responses to HER2 inhibitors have been poor. Next generation sequencing technologies in conjunction with testing using patient‐derived xenografts (PDX) allow validation of personalized treatments. Using a whole‐genome mate‐pair next generation sequencing (MPseq) protocol, we identified several high grade serous ovarian cancers (HGS‐OC) with DNA alterations in genes encoding members of the ERBB2 pathway. The efficiency of anti‐HER2 therapy was tested in three different PDX lines with the identified alterations and high levels of HER2 protein expression. Treatment responses to pertuzumab or pertuzumab/trastuzumab were compared in each PDX line WITH standard carboplatin and paclitaxel combination treatment. In all three PDX models, HER2‐targeted therapy resulted in significant inhibition of tumor growth compared with untreated controls. However, the responses in each case were inferior to those to chemotherapy, even for chemo‐resistant lines. When chemotherapy and HER2‐targeted therapy were administered together, a significant regression of tumor was observed after 6 weeks of treatment compared with chemotherapy alone. Post‐treatment analysis of these tissues revealed that inhibition of the ERBB2 pathway occurred at the level of phosphorylation and expression of downstream targets. In conclusion, while targeting of presumably activated ERBB2 pathway alone in HGS‐OC results in a modest treatment benefit, a combination therapy including both chemotherapy drugs and HER2 inhibitors provides a far better response. Further studies are needed to address development of recurrence and sensitivity of recurrent disease to HER2‐targeted therapy.

show abstract