Mutations

Cancer Genes open door to targeted treatments

In a discovery that could lead to more targeted and effective treatments for certain lung and prostate cancers, researchers at the University of Virginia School of Medicine have identified two new cancer-causing gene mutations – mutations that may be particularly susceptible to cancer-fighting drugs already approved by the federal Food and Drug Administration. One of the gene mutations also may play a key role in early menopause.

Anindya Dutta, MD, PhD, of the University of Virginia School of Medicine and...
Anindya Dutta, MD, PhD, of the University of Virginia School of Medicine and the UVA Cancer Center.
Source: University of Virginia Health System

‘The Perfect Hammer’

The discovery suggests that cancers with the newly discovered mutations in the MCM8 and MCM9 genes likely will respond extremely favorably to the same chemotherapy drugs that have already proven effective against breast cancers with the well-known BRCA1 and BRCA2 gene mutations.

“One of the biggest problems in cancer is that we hit everything with the same hammer, and consequently some cancers are responsive and others are not. Imagine if you could find the perfect hammer for the nail – the famous personalized therapy,” said lead researcher Anindya Dutta, MD, PhD, of the UVA Cancer Center. “If a patient has BRCA1 and BRCA2 mutations, then the perfect hammer is cisplatin and olaparib. Similarly, [for other cancers,] if you could break them up into those with mutations in MCM8 and MCM9, and then hit them hard with olaparib and cisplatin, we predict that there will be much better responsiveness.”

Missing DNA Repairmen

Dutta’s new research shows that the MCM8 and MCM9 genes produce proteins that play a critical role in homologous recombination, a method cells use to repair double-strand breaks in our DNA. Such breaks are thought to occur commonly -- perhaps thousands of times in each cell’s life -- but the vital repair proteins appear to be missing in cancers with MCM8 and MCM9 mutations. That defect could be the cancer cells’ downfall, theoretically making them “superbly sensitive” to cisplatin and other drugs already developed to battle BRCA1 and BRCA2 mutations, said Dutta, chairman of UVA’s Department of Biochemistry and Molecular Genetics.

As of now, there is no commercially available diagnostic test for the MCM8 and MCM9 mutations, though they could be revealed via whole genome sequencing. Dutta, however, says that a much simpler test can be designed; he’d also like to see a clinical trial to determine the effectiveness of cisplatin and olaparib in battling cancers with the MCM8 and MCM9 mutations.

Dutta’s research also notes the correlation of genetic inactivation of the MCM8 gene and the early onset of menopause, also known as premature ovarian failure. That will give scientists a new avenue to explore as they seek to better understand the condition.


Source: University of Virginia Health System

15.10.2015

Read all latest stories

Related articles

Photo

Brain cancer

Typical mutation in cancer cells stifles immune response

The exchange of a single amino acid building block in a metabolic enzyme can lead to cancer. In addition, it can impair the immune system. It thus blocks the body’s immune response in the battle…

Photo

DNA manipulation

Chaos in cancer cells: Mysterious gene transcripts after therapy

Drugs that are used in cancer therapy to erase epigenetic alterations in cancer cells simultaneously promote the production of countless mysterious gene transcripts, scientists from the German Cancer…

Photo

Research

New Biomarker for cancer immunotherapy?

The Ligand PD-L1 is one of the most important targets for cancer immunotherapy with checkpoint inhibitors. But not all tumors have sufficient quantities of PD-L1 ligands on their surface. Scientists…

Related products

Agena Bioscience - MassARRAY Colon Panel

Amplification/Detection

Agena Bioscience - MassARRAY Colon Panel

Agena Bioscience GmbH
Eppendorf – BioSpectrometer fluroescence

Research Use Only (RUO)

Eppendorf – BioSpectrometer fluroescence

Eppendorf AG
Eppendorf – Mastercycler nexus X2

Research Use Only (RUO)

Eppendorf – Mastercycler nexus X2

Eppendorf AG
Eppendorf – μCuvette G1.0

Research Use Only (RUO)

Eppendorf – μCuvette G1.0

Eppendorf AG
Orion Diagnostica Oy – Orion GenRead

Amplification

Orion Diagnostica Oy – Orion GenRead

Orion Diagnostics Oy