Scientists have crafted an exceptional cancer drug that shows promise in defeating various solid cancer tumors without harming healthy cells. Dubbed AOH1996, this newly discovered molecule takes aim at a protein commonly found in most cancers, which fuels the growth and multiplication of tumors within the body.
The significance of this achievement cannot be overstated, as the targeted protein, known as proliferating cell nuclear antigen (PCNA), was once considered “untouchable” by medical means.
Rigorous laboratory testing on 70 different cancer cells, encompassing breast, prostate, brain, ovarian, cervical, skin, and lung cancer, demonstrated the drug’s effectiveness across the board.
This medical breakthrough is the culmination of two decades of relentless research and development conducted at the prestigious City of Hope Hospital in Los Angeles, recognized as one of the largest cancer centers in the United States.
Targeted efforts to cure cancer
President Joe Biden has made curing cancer a top priority, and in 2022, he launched the Cancer Moonshot initiative with the ambitious goal of halving the cancer death rate within the next 25 years.
However, his recent claim that his administration had “ended cancer as we know it” faced criticism, despite indications that cancer death rates are showing signs of slowing down.
According to the latest study published in the journal Cell Chemical Biology, the new drug underwent rigorous testing on over 70 different cancer cell lines, along with several normal human cells used as a control group, which didn’t have cancer.
Remarkably, the molecule exhibited a targeted approach, selectively eradicating cancer cells by disrupting their normal reproductive cycle. This disruption prevented cells with damaged DNA from dividing and halted the replication of faulty DNA.
The combined effect of these actions resulted in the cancer cells dying off without causing harm to healthy cells in the process.
Replication of the results
The next critical phase involves replicating the results in human subjects. Currently, the drug is undergoing testing in a Phase 1 clinical trial at the City of Hope Medical Center.
Leading the research team is Dr. Linda Malkas, a professor in the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope, holding the esteemed position of M.T. & B.A. Ahmadinia Professor in Molecular Oncology.
Dr. Malkas explained how the molecule functions with remarkable precision, disrupting the replication and repair of DNA exclusively in cancer cells, while leaving healthy cells unharmed.
She elaborated on the uniqueness of their approach, stating that most targeted therapies typically focus on a single pathway, allowing cancer cells to adapt and develop resistance. In contrast, their drug directly targets a variant of the protein PCNA, present in cancer cells but not in healthy cells, making it a highly specific and effective treatment.
Drawing an analogy, Dr. Malkas likened their cancer-killing pill to a snowstorm that shuts down a key airline hub, preventing flights carrying cancer cells from departing.
Early results of the study
The early results have been promising, showing that the molecule can suppress tumor growth on its own or in combination with other cancer treatments without causing harmful side effects.
The development of this novel therapy stems from two decades of dedicated research and development. PCNA, in its mutated form, plays a crucial role in the DNA replication and repair processes within rapidly growing tumors, enabling cancers to grow and repair.
This is how the location of the proliferating cell nuclear antigen #PCNA looks in #HCC tissues. pic.twitter.com/EOl2pla0KP
— Antonio Silva-Gomez (@JASilvaG) December 8, 2019
Dr. Long Gu, an associate research professor and co-author of the study, emphasized that PCNA was previously considered “undruggable,” but City of Hope has managed to create an investigational medicine to target this challenging protein.
He explained that their research has unveiled PCNA as a potential contributor to replication errors in cancer cells. With their newfound ability to inhibit PCNA, the team aims to delve deeper into the process to develop personalized and targeted cancer treatments.
Mechanism of action of new drug
Notably, experiments have revealed that the investigational pill renders cancer cells more susceptible to chemical agents that cause DNA or chromosome damage, suggesting that AOH1996 could be utilized in combination therapies and new chemotherapeutics.
Moving forward, the researchers will continue to investigate the drug’s mechanism of action to further enhance its efficacy during the ongoing human clinical trial.
A press release accompanying the recent findings highlighted City of Hope’s groundbreaking history in translational research, including pivotal contributions to the development of synthetic human insulin and monoclonal antibodies, crucial components of widely used and life-saving cancer drugs such as trastuzumab, rituximab, and cetuximab.