The new combination of drugs holds promise for improved treatment of cervical cancer

A study led by the University of Texas Southwestern Medical Center has shown that a new combination of drugs slows the growth of cancer cells through an unexpected mechanism, which promises to improve the treatment
of cervical cancer.

Cervical cancer is the fourth largest cancer in women worldwide, with an estimated 600 000 new cases in 2020
.
Despite advances in screening, early diagnosis and cancer prevention, it remains the second leading cause
of cancer-related death among women aged 20 to 39 years.

When treating cervical cancer, most treatment options are combined with the chemotherapy drug cisplatin with other drugs
.
However, tumors may become resistant to cisplatin, which greatly hinders cisplatin use and suggests the need for alternative drug combinations to improve treatment outcomes
.

PARP inhibitors (PARPis), which can block the repair of DNA damage in tumor cells, have recently been approved by the US FDA as cancer treatment drugs, especially for gynecologic cancers
.
Researchers at the University of Texas Southwestern Medical Center found that the combination of cisplatin and PARP inhibitors was more effective at limiting the growth
of some cervical cancer cells.

The paper's corresponding author, Professor of Obstetrics and Gynecology and Pharmacology, W.
Smith Dr Lee Kraus said: "Our work shows that the combination of platinum-based therapies and PARP inhibitors can induce new cellular pathways in cancer cells and potentially open up new therapeutic opportunities
.
”

The researchers used a variety of cell lines representing different types of cervical cancer, including adenocarcinoma, epidermoid carcinoma, and squamous carcinoma
.
After treatment with PARPi, cisplatin, or a combination of both, they tested the growth and survival of the cells
.
They found that treatment with PARPi alone slowed cell growth
in adenocarcinoma and squamous cell carcinoma.
However, the combination of PARPi and cisplatin is more
toxic to cells than either drug alone.

In analyzing the mechanism of action, the researchers also showed that the combination of PARPi and cisplatin did not simply kill cancer cells by blocking the repair of damaged DNA in these cells
.
They found that when used in combination with cisplatin, PARP-1 stimulated the expression of certain genes that produced proteins that inhibit the cell cycle, block cell growth and division, and promote apoptosis
.
This mechanism has nothing to do with
the role of PARPi in enhancing DNA damage in cancer cells.

Dr.
Kraus said the UC Southwestern Medical Center's research team, which integrates the expertise of scientists and clinicians, has long worked to expand the potential
of PARPi in the treatment of gynecologic cancers.

The results were published in the journal Molecular Cancer Research
.
Other researchers involved in the study included Rebecca Gupte, Tulip Nandu, Ken Y.
Lin, and Jayanthi S.
Lea
.

Original search

Combinatorial Treatment with PARP-1 Inhibitors and Cisplatin Attenuates Cervical Cancer Growth through Fos-Driven Changes in Gene Expression