Scientists discover secret to promising new cancer drug

Australian researchers have resolved a mystery about how a promising new class of anti-cancer drugs, called nutlins, work - paving the way for improving the future of cancer treatment. Nutlins, which are in early clinical trials for treating blood cancers, sparked interest worldwide for their ability to stop cancer growth by activating the body's natural cancer-suppressing mechanism - a gene called P53 - while at the same time avoiding some of the damaging effects of chemotherapy. However, until now, it was unknown whether nutlins were killing the cancerous cells, or just suppressing them temporarily.

Dr Liz Valente, Dr Brandon Aubrey, Professor Andreas Strasser and colleagues from the Walter and Eliza Hall Institute have found the answer to the long-standing question of how nutlins work by discovering that nutlins cause cancer cells to self-destruct and not just go to 'sleep'.

The research, published in the journal Cell Reports, revealed that nutlins activated P53 to trigger programmed cell death (apoptosis) of blood cancer cells. This was identified through the presence of a protein called PUMA.

Dr Aubrey, who is also a clinical haematologist at The Royal Melbourne Hospital, said the discovery not only reinforced that nutlins were a promising new treatment for blood cancer, but also that it provided invaluable information for a more tailored approach to patient care.

"Our findings will help identify which patients are most likely to benefit from nutlins and which types of cancers are most likely to respond to nutlins as a treatment," Dr Aubrey said.

"Understanding in detail how the drugs work will help in the design of better clinical trials and bring the world closer to more precise and personalised medical treatments for cancer."

Professor Strasser said previous research around P53 showed the gene was like a natural 'guardian' of healthy cells in the body and was a major barrier to developing cancer.

"When functioning properly, P53 is activated in response to early cancerous changes in the cell," Professor Strasser said. "P53 acts by either halting the cell while repairs are made or by forcing the cell to die if it cannot be repaired.

"Without the 'help' of P53, a damaged cell can be allowed to multiply, leading to cancer development. P53 lies dormant in many types of cancer - that do not have mutations in P53 - and the nutlins work through re-awakening its activity."

Professor Strasser said knowing more information about what nutlins were capable of by identifying how nutlins were activating P53 to trigger cell death in cancers was a critical step towards developing more sophisticated treatments for cancer.

"By understanding how nutlins are killing cancer cells, we can begin to formulate their best possible use, including choosing the best partner drugs to combine the nutlins with," Professor Strasser said.

Dr Aubrey is a PhD student at the Walter and Eliza Hall Institute enrolled through The University of Melbourne's Department of Medical Biology. Professor Strasser is a joint division head in the Molecular Genetics of Cancer division at the Walter and Eliza Hall Institute.

The research was supported by the National Health and Medical Research Council, the Leukemia and Lymphoma Society, Cancer Council Victoria, the Leukaemia Foundation of Australia, the Victorian Cancer Agency and the Victorian Government Operational Infrastructure Support Scheme.

The Walter and Eliza Hall Institute is the research powerhouse of the Victorian Comprehensive Cancer Centre, an alliance of leading Victorian hospitals and research centres committed to controlling cancer.

Valente, Liz J. et al.
Therapeutic Response to Non-genotoxic Activation of p53 by Nutlin3a Is Driven by PUMA-Mediated Apoptosis in Lymphoma Cells
Cell Reports, DOI: http://dx.doi.org/10.1016/j.celrep.2016.01.059

Most Popular Now

Fasenra (benralizumab) receives US FDA approval fo…

AstraZeneca and its global biologics research and development arm, MedImmune, announced that the US Food and Drug Administration (FDA) has approved Fasenra (benralizumab)...

A great place to do great things: Developing game-…

Science has spoken: Abbott (NYSE: ABT) is, again, among the best science-based companies to work for in the world. For the 14th year, the journal Science today recognized...

Alzheimer's disease might be a 'whole body' proble…

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But research from the University of British Columbia and Chinese scie...

Cancer cells destroyed with dinosaur extinction me…

Cancer cells can be targeted and destroyed with the metal from the asteroid that caused the extinction of the dinosaurs, according to new research by an international col...

Novartis confirms leadership in multiple sclerosis…

Novartis today announced it will present 54 scientific abstracts from across its multiple sclerosis (MS) research portfolio at the 7th Joint European and Americas Committ...

Amgen and Novartis announce expanded collaboration…

Amgen (NASDAQ:AMGN) and Novartis announced an expanded collaboration with the Banner Alzheimer's Institute (BAI) to initiate a new trial - the Alzheimer's Prevention Init...

Transplanted hematopoietic stem cells reverse dama…

Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mous...

Novartis announces the planned acquisition of Adva…

Novartis announced today, that it has entered a memorandum of understanding with Advanced Accelerator Applications (AAA) under which Novartis intends to commence a tender...

'Precision Medicine' may not always be so precise

Precision Medicine in oncology, where genetic testing is used to determine the best drugs to treat cancer patients, is not always so precise when applied to some of the w...

China's out of control 'silent killer' affects one…

More than one-third of adults in China have high blood pressure - often dubbed the "silent killer" for its lack of symptoms - but only about one in 20 have the condition ...

New tissue-engineered blood vessel replacements on…

Researchers at the University of Minnesota have created a new lab-grown blood vessel replacement that is composed completely of biological materials, but surprisingly doe...

New US study reveals key reasons why millions of p…

Few of the more than 90 million Americans(1) with obesity are seeking and receiving long-term obesity care, according to new data from the Awareness, Care and Treatment I...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]