Designing efficient, individualised cancer medicines requires an understanding of how cancer develops. For many years, scientists have understood that certain kinds of gene mutations are the origin of cancer.

When operating regularly, tumour suppressor genes can prevent malignant cells from proliferating out of control and start the apoptosis, a type of cell death, process.

Tumour suppressor genes may become dysfunctional as a result of mutations, which could potentially promote the growth of cancer. In a recent study published in Cell Reports, researchers at the University of Colorado Anschutz Medical Campus described the discovery and characterisation of a novel protein involved in a mechanism that suppresses different types of tumours.

The tumour suppressor gene called TP53 effectively restricts the development and growth of many different tumour types across the human body, and it is the most frequently mutated tumour suppressor gene in human cancers. This gene encodes a protein called p53, which is both a potent inhibitor of cell proliferation and an inducer of apoptosis.

According to Zdenek Andrysik, PhD, assistant research professor of pharmacology at the University of Colorado School of Medicine and one of the authors in the paper, "In more than half of cancer cases, TP53 is not mutated, remaining instead in a dormant state. Accordingly, many research efforts have been devoted to the development of drugs that could reactivate this latent form of p53 for cancer therapy. However, most cancers respond to activation of p53 with these medications with a transient block in cell proliferation."

"A better response to these drugs would be cancer cell elimination via apoptosis. Therefore, it is critical for us to understand what other factors are required for effective p53-targeted cancer therapy."

To address this knowledge gap, Maria Szwarc, PhD, and Anna Guarnieri, PhD, former postdoctoral fellows in the department of pharmacology and co-leading authors of the paper, employed a multi-disciplinary experimental approach, including genetic screening using CRISPR technology, to disrupt all genes in the human genome one-by-one and pinpoint which genes are required for full p53 activation.

As a result, the screening identified the protein called FAM193A, about which very little was known, as a potent and widespread positive regulator of p53 activity.

"Our follow-up studies revealed that FAM193A is required for the stabilisation of the p53 protein and its functionality," Dr Szwarc explains.

"The results showed that FAM193A interferes with cellular factors that usually repress p53 function, the proteins MDM2 and MDM4, which are commonly overactive in cancers. We found that FAM193A can antagonise the MDM4 protein and thus unleash p53's ability to stop cancer cell proliferation and survival. In agreement with these findings, we documented that high levels of FAM193A found in certain tumour types are associated with a better prognosis for cancer patients."