Molecular diagnostics can be used for early detection of cancer, prognosis, and prediction of therapy efficacy. These tools also help us understand differences between cancers of the same histologic type. Molecular diagnostics are tests that determine the presence of biomarkers— cellular constituents that can be measured from blood, urine, tumor, or other samples. It is hoped that biomarkers will be able to provide information about the presence and prognosis of a cancer. Biomarkers could also help identify cancer earlier, particularly in people at increased risk, leading to improved survival.

Molecular Detection and Treatment of Testicular Germ Cell Tumors Advanced Through the Genomic Revolution

An increasing understanding of the molecular basis of cancer now enables molecular detection using biomarkers, as well as selection of patients likely to benefit from molecularly targeted treatment approaches. Research into genomic biomarkers in testicular germ-cell tumors has ushered in a new era of treatments for patients with these cancers.

Several classic protein-based germ-cell tumor markers have been used for decades in patients with testicular cancer. The tests, however, are not very accurate. In a 2019 study, investigators looked at serum levels of the genomic biomarker microRNA371 (M371) as a strategy to stage testicular germ-cell tumors and assess response to treatment. Prior studies of a test measuring this marker were encouraging, but additional studies were needed.

In a new study conducted this past year, the investigators demonstrated that the M371 test was very accurate (sensitivity of 90%, specificity of 94%) for predicting clinical stage, tumor size, and response to treatment of testicular germ-cell tumors.20 The results of this study mark a significant advance in the use of molecular biomarkers as effective tools for diagnosis and disease management. They represent an improvement over currently used tests (β-human chorionic gonadotropin and α-fetoprotein [AFP] for testicular cancers) that is expected to affect patient care going forward should M371 receive FDA approval.

First Biomarker-Driven Approach to Treatment of Metastatic Pancreatic Cancer

The BRCA gene is associated with DNA damage repair; thus, mutated BRCA in which DNA damage repair is hindered can lead to the development of cancer. BRCA mutations identified through genetic/molecular testing can serve as biomarkers for cancer. Biomarkers can also inform which therapy may be the most effective treatment. Germ-cell BRCA testing is already routinely done to detect families with high risk, as well as to identify patients with breast or ovarian cancer likely to benefit from olaparib.

Olaparib is an oral PARP (poly [ADP-ribose] polymerase) inhibitor. It works by blocking a process that repairs damage to DNA, which ultimately promotes cell death. The federally funded randomized phase III POLO trial (ClinicalTrials.gov identifier: NCT02184195)21 was designed to test treatment with olaparib as a maintenance strategy after the control of metastatic pancreatic cancer using first-line chemotherapy.

The trial enrolled 154 patients with metastatic pancreatic cancer who were identified as having germline BRCA mutation to receive olaparib or placebo following initial platinum-based chemotherapy. In this population of patients, olaparib significantly delayed cancer progression compared with placebo, with a median progression-free survival of 7.4 months compared with 3.8 months for the placebo group. Two years after initiating olaparib, pancreatic cancer in 22.1% of patients had not progressed, compared with 9.6% of those treated with placebo, in whom the cancer had not progressed. This study was funded in part by the NCI.

Germline Genetic Testing: ASCO PROVISIONAL CLINICAL OPINION

In January 2019, ASCO issued a Provisional Clinical Opinion (PCO) stating that germline genetic testing for cancer susceptibility—including testing for BRCA mutations—may be discussed with patients with pancreatic cancer even if there is no clear family history. For more details, view the PCO.  

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