After finishing a round of primary treatment, your doctor will likely consider putting you on a maintenance therapy regimen, which involves targeted therapy. One class of drugs that is usually considered for high-grade serous, endometrioid or clear cell carcinomas is PARP inhibitors.  PARP inhibitors affect the DNA synthesis and repair pathways in a cell and it has been found that mutations in genes that are involved in repair of DNA when it is damaged (the homologous repair pathway-most notable within this family are the BRCA1 and BRCA2 genes) render sensitivity to these drugs. Many of these mutations are germline mutations, or inherited mutations. However sometimes these mutations may be somatic mutations and hence testing tumour tissue can also be useful.

In addition to testing for mutations in these genes, we can also test for a genomic signature which assesses the effect of these mutations. The HRD ( Homologous Repair Deficiency) test thus measures not only mutations in genes, but also the genomic scar signature, which is a measure of the genomic instability of the tumour. Studies have shown that a high genomic instability score is associated with response to PARP inhibitors. In addition to BRCA mutations, mutations in other genes, and other mechanisms also lead to defective homologous repair, and HRD testing can identify these cases as well.

PARP inhibitors can be given as maintenance therapy following primary treatment, in early to late stage ovarian cancer, as well as later line therapy for metastatic ovarian cancer as well.

If you have advanced disease then testing for defects in the HRD pathway  i.e. testing for BRCA1/2 mutations or a genomic HRD test is useful for assessing likely response to a class of drugs known as PARP inhibitors. In addition to this, on rare occasions, tumours may contain a well-known mutation in the BRAF gene, which indicates possible response to a certain combination of drugs known as MEK inhibitors.  Genomic profiling using a large genetic panel can identify such mutations, as well as mutations in other genes for which drugs are being used in other tissues or are being explored and researched in clinical trials.

Sometimes a tumour, despite being given appropriate treatment, does not respond well to the therapeutic regimen. In such cases you and the clinician might want to consider other targeted therapy options if available. It may be useful to profile these tumours with a broad large panel of genes that are mutated across a variety of cancers as there may be a possibility that one of them is also mutated in your tumour. If such a gene is identified, it may open up additional avenues of treatment with targeted therapy. Hence,you and your doctor may consider Strand’s large panel genetic tests for such cancers if you would like to explore other potential treatment options. Large panel testing can also help determine your suitability for immunotherapy by measuring the Tumour Mutational Burden (TMB) and Microsatellite Instability (MSI). Both these are a measure of the immunogenicity of the tumour i.e. how well it can be recognized and attacked by the immune system. Large panels can also be used at the outset if you are interested in comprehensively understanding a tumour’s genetic makeup before starting treatment.