Small molecule drug combined with chemotherapy may deliver a synergistic benefit for colorectal cancer patients

January 8, 2016
A study led by Professor Chng Wee Joo from the Cancer Science Institute of Singapore at the National University of Singapore has demonstrated the efficiency of a small molecule drug, PRIMA-1met, in inhibiting the growth of colorectal cancer cells.

A study led by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has demonstrated the efficiency of a small molecule drug, PRIMA-1met, in inhibiting the growth of colorectal cancer cells. Colorectal cancer is the cancer of the large intestine (colon and rectum) and is the most common cancer in Singapore.

PRIMA-1met is a compound that has been shown in previous studies to activate mutant p53, a tumour suppressor gene, and promotes death of cells. The compound has demonstrated promising preclinical activity in various cancer types and shown good drug safety profiles.

"Colorectal cancer is known for its poor long term survival rates among adults. Given the excellent safety profile of PRIMA-1met, coupled with its minimal and fully reversible side effects, we are optimistic that the development of this drug as a targeted therapeutic approach against , together with chemotherapy, holds good potential for patients," said Professor Chng Wee Joo, Deputy Director and Senior Principal Investigator at CSI Singapore, who led the research.

The NUS team published their findings online in October 2015 in the journal Oncotarget.

Reactivating the "Guardian of the genome"

is also known as the "Guardian of the genome" as it codes for an important protein that helps to stabilise and repair genomes. When mutations occur in p53, the cells become more susceptible to damage and hence turn cancerous. Nearly half of colorectal cancer patients have mutations in the p53 gene. In this study, the NUS team found PRIMA-1met to be most effective in killing colorectal cancer cells that contain the mutated p53.

Unlike most anti-cancer drugs which works by inducing damage to DNA and often has serious side effects, PRIMA-1met is more favorable as it restores the structure and function of the mutated p53 and specifically promotes the death of .

Currently, PRIMA-1met is part of a Phase I/II clinical trial in hematologic malignancies and prostate cancer. In such clinical trials, the drug of interest is given to a group of patients with hematological and solid cancers to test for its safety, efficacy, and effectiveness, as well as to identify the dosage range and potential side effects.

Moving forward, Prof Chng and his team plan to test if the combination of PRIMA-1met, with anticancer drugs such as Fluorouracil and Oxaliplatin, which are commonly used for the treatment of colorectal cancer, will optimise the results of chemotherapy.

Explore further: Inhibiting protein fibers that cause Alzheimer's and Parkinson's diseases points toward ovarian cancer treatment

More information: PRIMA-1met (APR-246) inhibits growth of colorectal cancer cells with different p53 status through distinct mechanisms DOI: 10.18632/oncotarget.5385

Related Stories

Inhibiting protein fibers that cause Alzheimer's and Parkinson's diseases points toward ovarian cancer treatment

January 7, 2016
UCLA scientists have developed a promising novel method to treat gynecologic tumors. The approach focuses on a protein called p53, which is commonly mutated in women who have high-grade serous ovarian cancer, the deadliest ...

Gene thought to suppress cancer may actually promote spread of colorectal cancer

January 4, 2016
A gene that is known to suppress the growth and spread of many types of cancer has the opposite effect in some forms of colorectal cancer, University of Missouri School of Medicine researchers have found. It is a finding ...

Reducing resistance to chemotherapy in colorectal cancer by inhibition of PHD1

August 19, 2015
Scientists at VIB and KU Leuven have shown that blocking the PHD1 oxygen sensor hinders the activation of p53, a transcription factor that aids colorectal cancer (CRC) cells in repairing themselves and thus resisting chemotherapy. ...

New method characterizes structure of protein that promotes tumor growth

April 13, 2015
Moffitt Cancer Center researchers have developed a new method to identify a previously unknown structure in a protein called MDMX. MDMX is a crucial regulatory protein that controls p53 - one of the most commonly mutated ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.