Genetic Analysis May Offer New Approach to Treating Ovarian Cancer

Article

California researchers are now suggesting that analyzing copies of genes may point to new treatments for ovarian cancer as well as for other tumor types. The researchers contend that targetable genetic changes in tumors should not be limited to mutations.

California researchers are now suggesting that analyzing copies of genes may point to new treatments for ovarian cancer as well as for other tumor types. The researchers contend that targetable genetic changes in tumors should not be limited to mutations. Instead, they are focusing on an alteration that result in the loss or gain in a copy of a gene.

In a paper published February 15 in Nature Communications, Delaney et al. describe the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes. Ovarian cancer in particular is fraught with these alterations, with more than 60% of genes affected. When the team analyzed ovarian cancer using HAPTRIG, the pathway that stood out was autophagy, which is a natural process of cell death that helps maintain normal cellular health. Looking at 187 pathways, autophagy was found to be the most significantly disrupted by coincident gene deletions.

“When most people think about cancer genetics, they think about single key mutations that foster tumor formation, very specific things like the BRCA genes,” said lead study author Joe Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center in San Diego. “These changes are often referred to as tumor drivers but these are not the only deviations that impact cancer growth. We explored other possibilities.”

The researchers used a combination of existing US Food and Drug Administration approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models, even among cells resistant to standard chemotherapy.

Human ovarian cancer cells were found to be highly sensitive to challenge with autophagy-targeting agents, suggesting a new approach to treating this tumor type. The combination of drugs appeared to be less toxic than standard chemotherapy and the combination was relatively inexpensive. The researchers contend these agents warrant further investigation.  

They note that more than 90% of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. Currently, the researchers are providing a free web tool to allow clinicians to perform a HAPTRIG analysis on 21 cancer types. The researchers theorized that evaluating the copy-number landscape of a tumor may help lead to improved outcomes. With further work, these findings could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well, according to the authors.

Related Videos
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Developing novel regimens may continue to improve survival outcomes of patients with advanced cervical cancer following the FDA approval of pembrolizumab and chemoradiation, says Jyoti S. Mayadev, MD.
Treatment with pembrolizumab plus chemoradiation appears to be well tolerated with no detriment to quality of life among those with advanced cervical cancer.
Jyoti S. Mayadev, MD, says that pembrolizumab in combination with chemoradiation will be seamlessly incorporated into her institution’s treatment of those with FIGO 2014 stage III to IVA cervical cancer following the regimen’s FDA approval.
Domenica Lorusso, MD, PhD, says that paying attention to the quality of chemoradiotherapy is imperative to feeling confident about the potential addition of pembrolizumab for locally advanced cervical cancer.
Guidelines from the Society of Gynecologic Oncology may help with managing the ongoing chemotherapy shortage in the treatment of patients with gynecologic cancers, according to Brian Slomovitz, MD, MS, FACOG.
Interim data reveal favorable responses in patients with low-grade serous ovarian cancer treated with avutometinib plus defactinib, according to Susana N. Banerjee, MD.
Brian Slomovitz, MD, MS, FACOG, notes that sometimes there is a need to substitute cisplatin for carboplatin, and vice versa, to best manage gynecologic cancers during the chemotherapy shortage.
Findings from the phase 3 MIRASOL trial support mirvetuximab soravtansine as a standard treatment option for platinum-resistant ovarian cancer, according to Ritu Salani, MD.
Trastuzumab deruxtecan appears to elicit ‘impressive’ responses among patients with HER2-positive gynecologic cancers regardless of immunohistochemistry in the phase 2 DESTINY-PanTumor02 trial.
Related Content