Researchers at City of Hope, a leading cancer research and treatment organisation in the United States, have developed a new chemotherapeutic drug candidate that has shown promise in “annihilating” various types of cancer cells in lab and animal testing while sparing healthy cells.
Tested on a variety of cancer types, including but not limited to breast, prostate, brain, ovarian, cervical, skin, and lung cancers, the molecule dubbed AOH1996 disrupted DNA replication and repair in cancer cells, a method previously thought impossible.
In a paper published in Cell Chemical Biology, the researchers say that the molecule performed well in pre-clinical toxicity testing in animals (mice and dogs) and that a phase-1 clinical trial is in progress in the hope of developing it into a therapeutic for humans.
“Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” Linda Malkas, professor at City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics, said in a statement.
AOH1996 targets a protein called proliferating cell nuclear antigen (PCNA) which, in cancer cells, becomes hyperactive, causing them to grow and multiply uncontrollably leading to tumour formation.
“Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells,” Malkas explains.
PCNA was previously considered difficult or nearly impossible to target with drugs. Its crucial role in cancer cell growth and proliferation made it challenging to design drugs that could effectively inhibit its activity without causing harmful effects on healthy cells.
The AOH1996 molecule acts like a specialised lock that can selectively target and jam the hyperactive PCNA protein only in cancer cells. By doing so, it stops the excessive replication in cancer cells, causing them to self-destruct and eliminate the tumour without causing significant damage to normal cells.
“No one has ever targeted PCNA as a therapeutic because it was viewed as ‘undruggable,’ but clearly City of Hope was able to develop an investigational medicine for a challenging protein target,” said Long Gu, lead author of the study and an associate research professor in the Department of Molecular Diagnostics and Experimental Therapeutics at Beckman Research Institute of City of Hope.
The researchers also say that the molecule minimises common side effects associated with conventional chemotherapy.
These promising early results have sparked a wave of hope among both researchers and individuals with cancer, offering new prospects for those who were previously left with limited treatment options. The phase-1 clinical trial will now show the drug’s potential in the real-world and its effectiveness in treating individuals who have not responded well to standard treatments.
