Therapeutic options for mucinous ovarian carcinoma

Abstract

Objective. Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents.

P53 and PIK3CA Mutations in KRAS/HER2 Negative Ovarian Intestinal-Type Mucinous Carcinoma Associated with Mature Teratoma

“…In addition, HER2 amplification is also common in mucinous carcinomas, occurring in about 20% of cases and suggested HER2-targeted therapy as a potential option for HER2 amplified advanced or recurrent disease [ 11 ]. Mucinous carcinomas without KRAS mutation and/or HER2 amplification (KRAS/HER2: -) occur with a variable frequency according to the populations tested with an average of 10% in agreement with two previous studies [ 8 , 10 ]. Among the HER2/KRAS negative cancers, only one study was able to demonstrate on four tested cases, the presence of various additional mutations (CDKN2A, P53, BRAF, FGFR2, and STK11) [ 8 ].…”

“…Lastly, if the prognosis of stage 1 mucinous carcinomas remains excellent especially in tumors with an expansile pattern, infiltrative subtypes are more aggressive with local recurrences and/or lymph node involvements and classical adjuvant therapies (mainly carboplatin, paclitaxel,…) give unconstant effects [ 10 ]. Therefore, personalised molecular therapeutic strategies (antiestrogens, HER2 targeted therapies, RAS/RAF inhibitors, KRAS inhibitors, P53 reactivators, PI3-kinase inhibitors,…) will become crucial in the future as an alternative/complement to conventional chemotherapy [ 2 , 10 ]. These last years, in ovarian carcinomas associated with BRCA1/2 mutations, poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) (olaparib, niraparib, veliparib,…) demonstrated evident improvements in progression-free survival [ 16 – 18 ].…”

“…Genotypically, KRAS gene mutation is the most common gene alteration found in these tumors. KRAS mutations have been described as well in benign than in malignant mucinous ovarian tumors, suggesting that it probably plays a major role in the progression from benign to malignant phenotype [ 2 , 8 – 10 ]. Other mutations including PIK3CA, PTEN, BRAF, EGFR, KIT, STK11, CDKN2A, and P53 genes have also been described mostly in invasive mucinous carcinomas suggesting that these mutations take place belatedly in ovarian mucinous carcinogenesis [ 2 , 8 ].…”

Ovarian Cancer: Molecular Classification and Targeted Therapy

“…The predominant mutation present in MOCs is KRAS mutations reported in 66% of cases [79,80]. A recent large cohort study identified many other mutations in MOCs besides KRAS in varying degrees which are TP53 mutation, HER2 amplification (a member of the epidermal growth factor receptor family), PIK3CA/PTEN (regulator of PI3K-PTEN-AKT pathway), BRAF mutation, CTNNB1/APC mutations (regulator of Wnt-signaling pathway), and ARID1A mutation (a member of the SWI/SNF family) [80,79]. One of the potential drugs for the treatment of MOCs is 5-fluorouracil.…”

The Landscape and Therapeutic Implications of Molecular Profiles in Epithelial Ovarian Cancer

“…Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutation (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (see below) may not be effective in mucinous ovarian cancer, as only one out of 191 had a high homologous recombination deficiency score [23,35].…”