IRVING, Texas, March 29, 2015 /PRNewswire/ -- Caris Life
Sciences® today announced the presentation of two studies in which
Caris Molecular Intelligence®, the company's panomic, comprehensive
tumor profiling service, found that molecular similarities and
differences between several rare and difficult to treat
gynecological cancers may inform targeted treatment strategies that
have the potential to improve patient outcomes. These studies were
presented today during Poster Session B at the Society of
Gynecologic Oncology (SGO) 2015 Annual Meeting on Women's Cancer in
Chicago, Ill.
In each of these studies, conducted in collaboration with
researchers from the Cleveland Clinic, Caris Molecular
Intelligence® was used to compare uterine papillary serous
carcinoma and ovarian serous carcinoma, and epithelial ovarian
cancer and endometrial cancer, respectively. Caris Molecular
Intelligence's multi-platform profiling approach includes gene
sequencing (next-generation sequencing [NGS] and Sanger), protein expression analysis
(immunohistochemistry [IHC]), and gene copy number analysis
(chromogenic or fluorescence in situ hybridization
[CISH or FISH]). Investigators used these methods to examine tumor
samples for underlying molecular alterations that may yield
insights into potentially overlapping and different therapeutic
options for patients with these tumor types.
"In each of these studies, Caris Molecular Intelligence enabled
researchers to examine the molecular diversity, and in some cases
similarities, of each of these cancers providing information needed
to better understand variations in molecular pathways for
optimizing treatment selection," said Sandeep K. Reddy, M.D., Chief Medical Officer at
Caris Life Sciences, and a co-investigator in each of the two
studies. "We hope to further clarify the differences and
similarities observed in future studies, and to use the accumulated
evidence to inform evolving treatment paradigms in gynecologic
cancer."
Uterine Papillary Serous Carcinoma versus Ovarian Serous
Carcinoma
Researchers used Caris Molecular Intelligence® to
evaluate 240 uterine papillary serous carcinoma (UPSC) and 1,587
epithelial ovarian serous carcinoma (EOC-S) samples, and to compare
the molecular profiles of the two cancer subtypes.
The tumor suppressor gene TP53 was the most commonly mutated
gene in both UPSC and EOC-S (76% vs. 69%) samples. UPSCs were more
likely than EOC-S samples to harbor mutations in the oncogenes
PIK3CA (29% vs. 2%), FBXW7 (12% vs. 1%), KRAS (9% vs. 5%), the
tumor suppressor protein PTEN (7% vs. 1%), and CTNNB1 (2% vs.
0%).
"Whereas uterine papillary serous carcinoma appears to have a
distinct mutation profile, indicating higher activity of the
PI3K/PTEN/mTOR pathway, we saw no differences between uterine
papillary and ovarian serous carcinomas in alteration of the
homologous recombination pathway," remarked principal investigator
Robert Debernardo, MD, Gynecologic
Oncologist and Director of Minimally Invasive Surgery at the
Cleveland Clinic Ob/Gyn & Women's Health Institute. "Also
noteworthy was the overexpression of topoisomerase 2A and other
markers, although these findings need to be correlated with outcome
and response to chemotherapy."
There were no differences between UPSC and EOS-C in the rates of
mutation of APC, ATM, BRAF, and AKT1. IHC analysis showed
overexpression of the multidrug resistance protein 1 (MRP-1, 88%
vs. 83%), the programmed cell death protein 1 (PD-1, 68% vs. 68%),
PTEN (56% vs. 58%), topoisomerase 1 (TOPO1, 36% vs. 40%), and
progesterone receptor (PR, 32% vs. 30%) in both UPSC and EOC-S
samples. Methylguanine-DNA methyltransferase (MGMT) was more
frequently expressed in EOC-S than in UPSC (80% vs. 53%).
Conversely, IHC analysis showed that UPSC samples had higher
expression of topoisomerase 2A (TOPO2A, 89% vs. 69%), estrogen
receptor (ER, 60% vs. 53%), and ribonucleotide reductase M1 (RRM1,
35% vs. 27%) than did EOC-S samples. Similarly, CISH/FISH analysis
indicated higher expression of HER2 (17% vs. 4%) and HER2/neu (10%
vs. 2%) in UPSC than in EOC-S, respectively.
Epithelial Ovarian Cancer versus Endometrial
Cancer
Using Caris Molecular Intelligence, Dr. Haider Mahdi and colleagues also evaluated 9,193
epithelial ovarian cancer (EOC) and 3,133 endometrial cancer (EC)
specimens as a means to identify potential treatment strategies for
each malignancy. TP53, which has been implicated as a driver
mutation in both cancer types, was the most mutated gene in EOC
(61%) and EC (43%) samples. Compared to the TP53-mutated tumors,
TP53 wild type tumors carried significantly higher mutation rates
in PTEN, PIK3CA, KRAS, and CTNNB1, indicating higher activation of
the PI3K, MAPK, and Wnt pathways in TP53 wild type cohorts in both
cancer types.
Notably, in EC samples, TP53 wild type cases showed
significantly higher expression of ER (73% vs. 49%), PR (61% vs.
29%), and PD-L1 (33% vs. 14%), while TP53-mutated tumors showed
significantly higher HER2 amplification (10% vs. 1%) and expression
(7% vs. 1%); these associations were absent in the EOC samples. In
contrast, in EOC samples, TP53 wild type tumors carried three times
the cMET expression (29% vs. 9%), while BRCA1 and 2 mutations were
significantly higher in TP53-mutated cases (39% vs. 23%), but this
difference was not seen in EC tumors.
"Our results reveal the genetic heterogeneity of gynecological
cancers and suggest an increased benefit of targeting the PI3K,
MAPK, and Wnt pathways in TP53 wild type tumors in both epithelial
ovarian cancer and endometrial cancer," said Dr. DeBernardo. "While
hormonal and immunomodulatory therapies may be of particular
interest for patients with TP53 wild type endometrial cancer,
Her2-targeted therapies may benefit patients with TP53-mutated
endometrial cancer. For women with epithelial ovarian cancer,
cMET-targeted therapies and PARP inhibitors may be of particular
interest for treating TP53 wild type and TP53-mutated tumors,
respectively."
About Caris Life Sciences® and Caris Molecular
Intelligence®
Caris Life Sciences® is a leading
biotechnology company focused on fulfilling the promise of
precision medicine through quality and innovation. Caris Molecular
Intelligence®, one of the industry's leading tumor profiling
services with more than 70,000 patients profiled, provides
oncologists with the most potentially clinically actionable
treatment options available to personalize cancer care today. Using
a variety of advanced profiling technologies to assess relevant
biological changes in each patient's tumor, Caris Molecular
Intelligence connects biomarker data generated from a tumor with
biomarker-drug associations supported by evidence in the relevant
clinical literature. The company is also developing Carisome® TOP™
technology, a revolutionary and proprietary blood-based profiling
platform for diagnosis, prognosis, and theranosis of cancer and
other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers
services throughout Europe, the
U.S., Australia and other
international markets. To learn more, please visit
www.CarisLifeSciences.com.
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