Fetal and Maternal Medicine

Biography

Biography: Andre M Murad

Abstract

The two most important scientific developments of the past decade regarding therapies for patients with non-small cell lung cancer (NSCLC) are the ability to exploit particular genetic mutations with targeted therapies and the discovery of drugs that can help the patient's own immune system attack the cancer. Despite these advances, many patients do not yet benefit from either approach. To maximize patient benefit, clinicians and pathologists will need to rationally apply the growing scientific knowledge to best characterize a patient's tumor and possible driver mutations. A growing understanding of host-tumor immune interactions will hopefully help expand our therapeutic options. The still elusive identification of immunotherapy biomarkers will hopefully help identify patients most likely to derive a therapeutic response to immune checkpoint inhibitors, and promises to be an important field of study for years to come. More recent studies have shown that patients with high mutational burden NSCLC treated with anti-PD-1 presented a lower likelihood of progressive disease. Further analyses have suggested that taking into account mutational process and intratumoral heterogeneity could improve the prediction. Recent studies have described the incidence of MSI across a broad cancer spectrum using computational software programs and NGS data. Some trials have documented that solid tumors such as gastroesophageal and breast cancer with mismatch repair deficiency (dMMR) treated with immunotherapy resulted in remarkable responses. These articles are highly relevant because the US Food and Drug Administration (FDA) approved pembrolizumab in May 2017 for the treatment of all unresectable or metastatic cancer with MSI/dMMR irrespective of tissue origin. It was the first time that any therapy had been approved for cancers that share a specific genetic feature irrespective of site of origin. Furthermore, in late July, nivolumab was approved for MSI/dMMR metastatic colorectal cancer. The FDA approvals are based on studies showing disease control rates of 70% to 90% in patients with colorectal cancer and noncolorectal MSI/dMMR cancers, most of whom with disease that was refractory to standard chemotherapy upon entering these trials.