Caris Molecular Intelligence™ Identifies Large Number of Actionable Biomarkers in Urothelial Carcinoma (UC)

-- Results, Published in Clinical Genitourinary Cancer, Offer Key Insights and Potential New Treatment Strategies for Patient Population with Limited Drug Options

IRVING, Texas, Oct. 2, 2014 /PRNewswire/ -- Caris Life Sciences®, a leading biosciences company focused on fulfilling the promise of precision medicine, announced the publication of a study in which Caris Molecular Intelligence™, the company's comprehensive tumor profiling service, was used to identify actionable biomarkers in urothelial carcinoma (UC), a type of urinary cancer historically associated with poor prognosis and few treatment options. The study's results, published online in Clinical Genitourinary Cancer, may expand the range of treatment options for patients with UC, potentially leading to improved treatment outcomes.

Using Caris Molecular Intelligence's multi-technology approach, including immunohistochemistry (IHC), in situ hybridization (ISH), and gene sequencing (next-generation and Sanger sequencing) analysis, 592 locally advanced or metastatic UC tumors were studied, with 463 (87.5%) cases of bladder UC, 74 (12.5%) of non-bladder UC (renal pelvis, ureter, urachus, urethra), and 55 other histotypes (27 adenocarcinomas, 17 squamous cell carcinomas, 11 small cell carcinomas) reviewed respectively. This research identified a large number of biomarker aberrations that may help oncologists tailor treatment using conventional chemotherapies and targeted therapies not currently recommended for patients with this cancer. Specifically, multi-technology profiling was able to find 43 different therapeutic options across 98% of cases of bladder and non-bladder UC. As a group, bladder UCs exhibited higher levels of actionable biomarkers, suggesting that UCs from different primary sites and non-UCs are driven by different molecular pathways.

"This research clearly demonstrates the value of multi-platform molecular profiling in the community setting, helping to identify potential treatments that might not have been considered for underserved patient populations like those with UC," said Nicholas J. Vogelzang, M.D., US Oncology Research Comprehensive Cancer Centers, Las Vegas, Nev., and an investigator on this study. "For these patients, the results may be used to select treatment regimens depending on the cancer's site of origin, using NCCN-recommended therapies as well as therapies not currently approved for UC, but approved for other tumor types."

Urothelial cancer is the most common variant of urinary cancer, the second-most common genitourinary malignancy after prostate cancer, and the fourth-most common cancer in men. Whereas most urothelial cancers originate in the bladder, in rare cases these tumors may arise in the urethra, ureter, prostate, or renal pelvis. Approximately 25 to 30 percent of patients with UC present with muscle-infiltrating tumors with substantial potential for further disease progression, metastases and death. Patients with advanced UC are considered to have limited therapeutic options, and are not routinely offered individualized, targeted therapies based on molecular profiling.

Select highlights from this clinical study include:

• MP of UC showed high overexpression of TOPO2alpha, PIK3CA, and PTEN alterations in nonbladder (27%) and bladder UC (21%), and rare gene mutations across subtypes
• Compared with non-bladder UC, bladder UC consistently exhibited more frequent abnormal protein expression, including:
  • HER2 (10% vs. 3%; P = 0.04)
  • c-Kit (11% vs. 5%)
  • c-Met (25% vs. 8%)
  • AR (16% vs. 6%)
  • MGMT (63% vs. 43%)
  • RRM1 (32% vs. 11%)
  • SPARC (69% vs. 33%)
  • TOPO1 (63% vs. 39%)
• Bladder UC also exhibited increased amplification of HER-2 (12% vs. 2%; P = 0.06), compared to non-bladder UC

"We believe this study's identification of large numbers of actionable targets in UC encourages more widespread use of molecular profiling in the oncology community, as a means to improve patient outcomes," noted Sandeep K. Reddy, M.D., Chief Medical Officer, Caris Life Sciences. "These results also further validate the findings of numerous other Caris studies, which collectively demonstrate that cancer is clearly a disease of the pathway, not necessarily the site of origin. Physicians need more information on the molecular make-up of each unique tumor to definitively and confidently select treatment, and multi-platform molecular profiling can offer key insights in this regard."

About Caris Life Sciences
Caris Life Sciences is a leading biosciences company focused on fulfilling the promise of precision medicine through quality and innovation.  Caris Molecular Intelligence™, the industry's first and largest tumor profiling service, provides oncologists with the most potentially clinically actionable treatment options available to personalize care today. Using a variety of advanced and clinically validated technologies, which assess relevant biological changes in each patient's tumor, Caris Molecular Intelligence correlates biomarker data generated from a tumor with biomarker/drug associations derived from the cancer clinical literature. The company is also developing a series of blood tests based on its proprietary Carisome® TOP™ platform, a revolutionary blood-based testing technology 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.