E. Teugels PhD

Parp inhibitors

Summary

Inhibition of Poly (ADP-ribose) polymerase 1 has relatively recently entered the clinic. The ground-breaking drug both scientifically and clinically was olaparib, but several other PARP inhibitors are in development. This treatment is the first to therapeutically exploit mutant recessive cancer genes. In this review we discuss the discovery of this treatment, the preclinical and clinical studies, as well as some future perspectives.

(BELG J MED ONCOL 2016;10(7):263–275)

Mixed adenoneuroendocrine carcinoma (MANEC) of the colon: molecular pathogenesis and treatment

We present the case of a 30-year-old male patient with a high grade neuroendocrine carcinoma and an adenocarcinoma developed in a tubulovillous adenoma of the colon, with diffuse liver metastasis. He underwent a right hemicolectomy and received four courses of postoperative chemotherapy with cisplatin and etoposide, followed by high dose chemotherapy with autologous stem cell support. After this treatment there was a complete biochemical and radiological remission. Now, 48 months after diagnosis the patient is alive and in unmaintained complete remission. The occurrence of a high grade neuroendocrine carcinoma in a low grade colon adenocarcinoma without any intermediate phenotypes was intriguing. Comparative exome sequencing of DNA from the malignant components revealed six somatic changes in cancer consensus genes. In both tumours, we detected mutations in APC and KRAS, as well as in BCL9 and FOXP1. Only in the neuroendocrine carcinoma component did we find a mutation in SMARCA4. All mutations were absent in germ-line DNA. The finding of several identical somatic mutations in both components in the subsequent exome sequencing supports a clonal relationship between the neuroendocrine carcinoma and the synchronous adenocarcinoma. We suggest that a mutation in SMARCA4A may be responsible for the abrupt transition to the aggressive neuroendocrine phenotype.

(BELG J MED ONCOL 2015;9(1):31–34)