October 15, 2011 (Vol. 31, No. 18)

Caris’ Molecular-Level Services Focus on Finding the Most Effective Cancer Therapies

Caris Life Sciences believes that the future of cancer treatment lies in an in-depth understanding of the genetic makeup of a patient’s tumor. David Halbert, CEO and chairman, started Caris in 2005 to offer the healthcare market advanced pathology services to diagnose various diseases including cancer. The company’s complete diagnostic, prognostic, and theranostic services provide physicians with detailed, customized information to help with treatment planning.

The Caris Target Now™ molecular profiling platform examines a patient’s tumor to detect specific biomarkers that can be targeted with available therapeutics. The genetic profile of an individual’s tumor is matched to information in the Caris database of 100,000 published clinical studies reviewed by experts at Caris.

A final report summarizes available therapies that are most likely to be effective, as well as therapies that are likely to be ineffective for the patient, based on their tumor’s unique molecular profile. The report contains the most relevant information available to help physicians select effective cancer therapies.

The U. S. spends $124 billion on cancer care. Patients who do not respond to standard therapies contribute to the increasing costs of care. “Our goal is to improve care and decrease costs by identifying molecular targets to improve treatment response rates,” says Les Paul, M.D., CTO.

Circulating microvesicles (cMVs) captured on the surface of a microsphere with associated fluorescent-tagged detection antibodies to proteins common to cMVs: The intensity of the fluorescent signal is used to indicate elevated levels of relevant circulating microvesicles.

Caris Target Now uses state-of-the-art techniques, including direct gene sequencing, fluorescent in situ hybridization (FISH), DNA microarrays, and mutational analysis, to examine tumor samples sent by physicians. Molecular profiling uncovers treatment targets that point to tumor-specific therapeutic agents, including treatments that are not routinely part of standard regimens or those that may not have been considered previously.

For instance, Herceptin® is known to benefit breast cancer patients with the Her2 gene. However, an estimated 20% of ovarian tumors, 19% of gastroesophageal tumors, and 11% of colorectal cancers also express the Her2 gene, and these patients may benefit from Herceptin, too.

“Physicians report case anecdotes about cancer patients who show tremendous responses to drugs not regularly prescribed for these types of tumors,” says Tom Spalding, chief marketing officer.

Colorectal cancer is another area where Caris Target Now is used. The standard treatment is determined by whether the KRAS mutation is present or absent. “We go one step further and analyze members of the EGFR pathway by sequencing both KRAS and BRAS,” says Dr. Paul. If these mutations are found, patients generally do not benefit from standard treatment with EGFR (epidermal growth factor receptor) inhibitors.

A pilot study reported in the November 2010 issue of the Journal of Clinical Oncology showed that cancer treatments tailored to a tumor’s unique genetic makeup (determined by Caris Target Now) increased progression-free survival in 27% of cancer patients with refractory disease. Molecular profiling, in particular, helps patients who have not responded to standard therapies or patients with rare or aggressive solid tumors.

To date, nearly 20,000 patient tumors have been profiled with Caris Target Now. In 2010, the number of molecular profiled cancer cases increased by 300%, and 1,000 patients each month receive personalized profiles of their tumors. “These statistics support the growth of understanding the importance of molecular targets in cancer care today.”

Carisome™, the company’s newest technology under development, uses a blood-based method to isolate circulating microvesicles that may help to diagnose cancer. Circulating microvesicles range from 40 nanometers to 1.5 microns in size. They are small lipid bilayered particles released from cells, including tumor cells. Different tumors release different circulating microvesicles, which carry unique biomarker signatures that represent their cell of origin.

Researchers at Caris are working on ways to isolate, capture, and count circulating microvesicles as potential diagnostic tools for prostate, lung, breast, and other solid tumors. The noninvasive blood-based test could eventually replace invasive tissue biopsies.

Additionally, technologies used in Caris Target Now and Carisome may help companies screen for biomarkers in drug trials. The Carisome platform could become a service tool to characterize tumor-derived biomarkers in blood samples rather than in tissue biopsies. “It’s a big challenge to get multiple biopsies from patients, which is a limiting factor in drug trials,” says Spalding.

The company started with a small group of pathologists who specialized in analysis of colonoscopy tissue using standard anatomical laboratory methods. The service, called Caris Path™, expanded to cover dermatology, hematology, urology, and oncology pathology services. Traditional anatomical pathology techniques are still used, but molecular targeting tools are integrated to improve outcomes.

Circulating microvesicle with associated surface and cytoplasmic proteins, mRNA, and miRNA

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