Phil Stafford
VP, Bioinformatics

Sequencing for Skin Cancers

While molecular sequencing in advanced stages of melanoma is accepted, the same is not true of other advanced cutaneous malignancies. Most common skin cancers, such as basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC), are indolent and easy to address via surgical modalities and localized radiation. However, cases are rising and therapy options are limited. In cSCC alone, the incidence ranges from 1 to 2.5 million cases annually in the United States, and continues to increase along with the associated morbidity and mortality. The rate of metastasis of tumors with high-risk features can surpass 20%, and deaths are estimated to exceed those from melanoma.

Systemic therapy options are limited for patients with regional and distant metastases in cSCC. While PD-1 inhibitors have recently been approved for use in advanced SCCs with reported response rates of up to 50 percent, a significant portion of these patients still have a suboptimal response. In many institutions, additional mutational analysis of progressive or recurrent tumors is not routinely performed as there are currently no established practice guidelines. Basket trials using NGS have not altered management practices of patients with advanced cSCC despite identifying molecular alterations.

At Caris Life Sciences, the sequencing of the whole exome and whole transcriptome demonstrates the personalized cancer care that is possible if clinicians are willing to investigate each patient and act on the data obtained. For every patient, a specimen is sequenced utilizing both whole exome (DNA) and whole transcriptome sequencing (RNA), generating a comprehensive molecular profile. The Caris platform evaluates the most important known alterations in the network of genes that have a role in the pathogenesis of cSCC such as TP53, CDKN2A, NOTCH1 and NOTCH2, EGFR and TERT as well the molecular pathways RAS/RAF/MEK/ERK and PI3K/AKT/mTOR. Furthermore, the analysis may identify genomic aberrations associated with treatment resistance.

In addition, Caris has developed a massive database, CODEai™, built for the discovery of new molecular targets. CODEai contains over 1000 advanced cSCCs that have failed treatment with first, second, and even third line therapies. The molecular sequencing platform and machine learning algorithms (available through FOLFIRSTai™ and GPSai™) applied to the big data generated can identify new targets for treatment in advanced cSCC – potentially leading to limited surgery/excision, improved quality of life, and increased overall survival. The Caris Precision Oncology Alliance (POA) is a collaborative research network using the sequenced molecular data to focus on the development of biomarkers and therapeutic agents for patients in the future. The POA is an international research enterprise, collaborating across medical and scientific disciplines with a singular goal in mind: the treatment of human disease.