SCIENTIFIC BACKGROUND

BRCA1, BRCA2, ERBB2, PIK3CA, PTEN, Fusion Genes: NTRK1, NTRK2, NTRK3, RET

Ovarian cancer accounts for about 3.2% of all malignant neoplasms in women and is responsible for 5.3% of cancer deaths. In most cases the tumors are diagnosed at an advanced stage, so that the relative 5-year survival rate is currently an average of 41%. Overall, 75% of all ovarian cancers are fast, aggressively growing tumors (high-grade serous carcinomas, mixed carcinomas and carcinosarcoma), which in turn are responsible for 90% of the mortality from ovarian cancer.

 

The risk of developing ovarian cancer increases with age and depends on various hormonal factors. In addition, familial clusters of certain tumor diseases (especially ovarian, breast, colon and/or endometrial carcinomas) represents an established risk factor. Independent of the family history or the age of the patient, the risk for a genetic predisposition is on average 20.8% (causal variants BRCA1 or BRCA2) or 25.8% (causal variants in BRCA1/2 or other risk genes). As a result, all women with ovarian cancer should be informed about the risk of a genetic predisposition and offered genetic counselling.

 

POSSIBLE THERAPIES

Patients with advanced epithelial ovarian cancer, carcinoma of the fallopian tube or primary peritoneal carcinoma (stage IIB-IV) receive platinum-based chemotherapy in combination with a taxane.

 

Olaparib (Lynparza®) has been approved by the EMA for maintenance therapy following a complete or partial response to first-line platinum-based chemotherapy, provided that a pathogenic or likely pathogenic variant in the BRCA1 or BRCA2 gene has been detected in the patient's tumor tissue or germline.

 

Olaparib is a PARP1 (poly(ADP-ribose)polymerase1) inhibitor that uses the principle of "synthetic lethality". Olaparib inhibits the repair of DNA single-strand breaks according to the base excision repair mechanism. These single strand breaks are transformed into double strand breaks by the collapse of the replication fork, which in turn are repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). If HR fails due to a mutation in a DNA repair gene involved in HR, such as BRCA1 or BRCA2, the error-prone NHEJ takes effect and the cells become apoptotic.

 

In recurrent platinum-sensitive ovarian/fallopian tube/peritoneal carcinoma with complete or partial response to platinum-containing therapeutics, olaparib can be administered as second‑line maintenance therapy regardless of the BRCA1/2 mutation status. Nevertheless, BRCA-mutated patients show a reduced risk of disease progression under Lynparza® compared to patients with an undetermined BRCA status (19.1 vs. 8.4 months).

 

TARGETED PANEL

BRCA1, BRCA2, ERBB2, PIK3CA, PTEN, Fusion Genes: NTRK1/2/3, RET, MSI

GENES

BRCA1, BRCA2, ERBB2, PIK3CA, PTEN, Fusion Genes: NTRK1, NTRK2, NTRK3, RET

How to order

LATEST ARTICLES

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more

Antimicrobial resistance (AMR) is one of the most pressing global health threats, and accurate identification and surveillance of multidrug-resistant...

Read more