In a paper published in The Lancet Oncology, an investigator-initiated study by Wake Forest oncologists provided strong preliminary evidence that the combination of CPI-613 with modified FOLFIRINOX is well tolerated and results in durable therapeutic responses in patients with advanced adenocarcinoma of the pancreas.
Retrospective review of patients treated at our institution indicates that clinical efficacy of this new combination therapy appears to be markedly higher than FOLFIRINOX alone. Our genomics characterization of the complete responders has identified potential genetic markers that will help us determine which patients would most benefit from this new combination therapy.
Tissue biopsy is the standard diagnostic procedure for cancer. Traditional tissue biopsy suffers limitations in its prognostic capability over the course of disease, most obviously as an invasive procedure with potential complications, but also with respect to probable tumor clonal evolution and metastasis over time from initial biopsy evaluation.
Recent work, including our recent publication from the Precision Oncology Initiative of Wake Forest, highlights circulating tumor DNA (ctDNA) present in the blood as a supplemental, or perhaps an alternative source of DNA to reveal the cancer mutational landscape. Importantly, this non-invasive approach may facilitate repeated monitoring of treatment response and disease progression, serving as a means to guide targeted therapies based on detected actionable mutations in patients with advanced or metastatic solid tumors. Notably, ctDNA is driving appreciable research interest and may herald a revolution in the range of genomic profiling and molecular mechanisms to be utilized in the battle against cancer.
African-Americans typically have worse outcomes from smoking-related cancers than Caucasians, but the reasons for this remain elusive. The Precision Oncology trial at Wake Forest Baptist enrolled 431 cancer patients from March 2015 to May 2016. The majority of the patients had advanced tobacco-related cancers – lung, colorectal and bladder – and 13.5 percent were African-American.
Both the Wake Forest Baptist and The Cancer Genome Atlas cohorts revealed a significantly increased mutation rate in the TP53 gene in the African-American groups studied. This data suggests that increases in TP53 mutation in African-Americans may be responsible for the observed resistance to chemotherapy and a poorer prognosis overall.
Additionally, the Wake Forest Baptist team identified other genes that were highly mutated in current and former smokers, regardless of race. These results provide strong evidence that genomic instability is a fundamental hallmark of cancer and the events underlying the regulation of genome stability are centered on interactions with environmental factors and lifestyle, such as smoking.