Researchers discover protein function that could improve chemotherapy in the future

December 17, 2020

Chemotherapy attacks all cells in our body and not just cancer cells, which is why patients undergoing the treatment often experience side effects such as physical weakness, hair loss and nausea. However, because cancer cells divide and spread faster than most normal cells, cancer cells are more sensitive to chemotherapy, which kills cells by inhibiting their ability to spread. Chemotherapy often targets and damages DNA so that cancer cells can no longer replicate their genome, which is the process of copying the genetic information, and stop the growth and die.

However, cancer cells may find ways to escape the chemotherapy. When attacked by chemotherapy, cells - including cancer cells - will try to repair or bypass the damage.

A group of researchers at the Faculty of Health and Medical Sciences, University of Copenhagen, are trying to figure out how cells repair or bypass the lesions induced by chemotherapy, in the hope to provide new methods to inhibit these repair processes and make the chemotherapy more efficient.

In a new collaborative work with different laboratories at the Center for Protein Research, Associate Professor Julien Duxin and his group have revealed a protein that seems to play a vital role in recruiting DNA key repair and signaling factors. If they are right, the discovery could be important for future chemotherapy treatment.

'We have found strong evidence that the protein RFWD3 is responsible for orchestrating the repair of different DNA lesions induced by chemotherapy. If we can inhibit this protein, we could potentially block cells from tolerating DNA lesions, which could lead to more effective chemotherapy in the future', says Julien Duxin, group leader at The Novo Nordisk Foundation Center for Protein Research.

Uncovering the knowledge gap

The findings, published in Molecular Cell, is the culmination of three years of research at the Duxin Group. The group focuses on understanding the basic principles of DNA replication and DNA repair which allow cells to repair genomic lesions like the ones induced by chemotherapy says Julien Duxin.

'Since the 1950s and the pioneer work from Sydney Farber, we have been treating cancer patients with different types of chemotherapeutic agents. These are extremely toxic agents, which have been approved in the clinic because they are effective at killing cancer cells. But the truth is that we still don't know how cells can repair the damage caused by the treatment. It is a huge knowledge gap, which we are trying to fill in with our fundamental research', he says.

Using egg extracts from African frogs, which contain the same repair factors than the ones present in our cells, the group was able to identify the protein RFWD3 as a critical coordinator of the repair events that happen when cells are replicating across from DNA lesions.

The group observed that the absence of the protein leads to a profound defect in recruitment of the components needed to repair and tolerate the damage.

'Repairing DNA lesions is a complex sequence of multiple events. Our goal is to identify the proteins at each event, which are essential to do this type of repair', says Julien Duxin.

Little is known about how repair works across different kinds of DNA damage. The group is now trying to set up simple systems so it becomes possible to molecularly study how these damages are repaired, Julien Duxin explains.

'We have very little knowledge about how most of these lesions caused by chemotherapy are repaired inside our cells. We are setting up different model systems to study this in detail and identify the key enzymes essential to this process. And by knowing those key enzymes we also get key targets that companies can aim to inhibit', he says.
The study 'The ubiquitin ligase RFWD3 is required for translesion DNA synthesis' is published in Molecular Cell.

University of Copenhagen The Faculty of Health and Medical Sciences

Related Chemotherapy Articles from Brightsurf:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.

Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.

Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

Male fertility after chemotherapy: New questions raised
Professor Delb├Ęs, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.

Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.

Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.

Read More: Chemotherapy News and Chemotherapy Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to