Caris Life Sciences has recently passed the milestone of profiling over 100,000 solid tumours using a multiplatform approach. As part of its continued dedication to share this huge experience with the global oncology community, Caris Life Sciences is in a unique position to provide insight into how tumour profiling can help find potential treatment options in rare and aggressive diseases. At the recent European Society for Medical Oncology (ESMO) meeting in Copenhagen Denmark from 07th-11th October, Caris showed results from 5 studies across different types of cancer, two of which were included in poster discussion sessions.
In a study conducted by Ang and colleagues at key academic centers across the Caris Centres of Excellence, differences across age groups in the molecular characteristics of hepatocellular cancer were described.1 Young adult HCC patients tend to be female and have lower androgen receptor expression than older patients. Their cancers may also be more responsive to chemotherapy based on less drug resistance protein expression. A higher proportion of CTNNB1 mutations in patients older than 40 years old suggest non–hepatitis B etiology. The frequency of actionable mutations also appears to increase with age of the patient.
A similar study was presented by Salem et al.: a comparison of younger versus older patients with pancreatic cancer.2 The study described slight differences in distribution of mutation frequencies among younger and older PC patients. More cKIT, CTNNB1, MLH1, NTRK1 and PTEN mutations were found in younger patients but these were all classified as variants of unknown significance, co–occurred with RAS or RAF mutations and are likely to be passenger events. The distribution of KRAS mutations is slightly higher in older PC patients. There was no survival difference between the two age groups.
Differences within a single cancer type are not driven only by demographic factors but were also shown to correspond to differences in histology and site of cancer. Comparison of the genetic profiles of epithelial ovarian cancers (EOCs) and primary peritoneal carcinomas (PPCs) revealed two distinct cancers.3 Significant increases in androgen receptor, EGFR and ER proteins were observed in PPCs while more EOCs expressed PD–L1, PR TOP2A and TS. Dysregulation of the PIK3CA/AKT/mTOR pathway appeared to be more common in EOCs while loss of TP53 is a more common event in PPC based on this cohort.
The ability of a multiplatform approach to identify treatment options in difficult to treat diseases was also described. Vranic and colleagues found that a substantial proportion of relapsed/refractory non–Hodgkin’s Lymphoma NHL and nearly all classical Hodgkin’s Lymphomas (cHL) expressed actionable biomarkers. Concordance between the anti–PDL1 clones SP142 and SP263 was excellent and both may be used for immunohistochemical detection of PD–L1. In situ hybridization assays may be particularly useful for determination of PD-L1 gene alterations in cHL.
Comprehensive profiling of tumor samples from a cohort of 20 patients with a rare cancer, olfactory neuroblastoma, found that targetable mutations are uncommon in this disease.5 Wnt and cKIT/PDGFRA pathway alterations are detected in rare cases and are potentially treatable using novel targeted therapies. The best option for these patients remains optimization and prioritization of cytotoxic chemotherapy options.
- Ang C, Shields A, Xiu J et al. Molecular analysis of hepatocellular carcinomas (HCC) from different age groups. Annals of Oncology vol 27; suppl6 – Abstract 618PD.
- Salem M, Philip P, Feldman R et al. Comparative molecular analyses of pancreatic cancer (PC): Younger vs. older patients (pts). Annals of Oncology vol 27; suppl 6 – Abstract 620PD
- Knipparth AM, Arguello D, Heinzelmann–Schwarz V. Molecular characterization and comparison of epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC). Annals of Oncology vol 27; suppl 6 – Abstract 880P.
- Vranic S, Jin J, Kimbrough J et al. PD–L1 status in refractory lymphomas. Annals of Oncology vol 27; suppl 6 – Abstract 921P.
- Gatalica Z, Ghazalpour A, Swensen J et al. Molecular profiling of locally advanced/metastatic olfactory neuroblastomas (Esthesioneuroblastomas) reveals novel therapeutic targets. Annals of Oncology vol 27; suppl 6 – Abstract 964P.