by ecancer reporter Janet Fricker

An in-depth genomic and molecular analysis of cervical cancer has revealed new molecular subtypes for cervical cancer that in future could be used to inform use of personalised therapies, reports the journal Nature.

The study represents the largest comprehensive genomic analysis of cervical cancer to date.

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide, accounting for 528,000 new cases and 266,000 deaths worldwide each year.

Although early cervical cancer can be treated with surgery or radiation, metastatic cervical cancer is incurable.

New therapeutic approaches are urgently needed.

As part of The Cancer Genome Atlas (TCGA) Research Network, Christopher Vellano and colleagues, from The University of Texas MD Anderson Cancer Center, Houston, characterised genetic and molecular alterations in primary frozen cervical cancer samples and blood taken from 228 women.

None of the subjects had undergone prior chemotherapy or radiotherapy.

The team identified five novel genes (SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2) that are significantly mutated in cervical cancer.

Furthermore, they identified amplifications in CD274 and PDCD1LG2, two genes encoding for well-known immunotherapy targets.

The findings also reveal new cervical cancer subtypes, including a set of endometrial-like cervical cancers that tend to involve HPV-negative tumours and have high frequencies of three specific genetic mutations.

Notably, the team found the BCAR4 gene is involved in cervical cancer.

The BCAR4 gene can be targeted indirectly with the drug lapatinib, commonly used in breast cancer.

“For the first time, we report distinct molecular pathways activated in cervical carcinomas caused by different HPV types, highlighting the biologic diversity of HPV,” write the authors.

“Together, these findings provide insight into the molecular subtypes of cervical cancers and rationales for developing clinical trials to treat populations of cervical cancer patients with distinct therapies.”

Source: Nature