PNAS The Link Between Tumor Stem Cells and Circadian Clock Proteins

The research team, led by the University of Southern California Keck School of Medicine, demonstrated that after current standard treatments, circadian clock proteins that help coordinate changes in body function throughout the day may play a key role
in the growth and proliferation of glioblastoma.

Dr.

As the most common brain cancer in adults, glioblastoma is an aggressive disease
.

The initial symptoms of glioblastoma include blurred vision, headache and nausea, and even seizures and personality changes
.

The researchers believe that the cancer recurs because a small number of cancer stem cells
are left behind after surgery, chemotherapy and radiotherapy.

Circadian clock dysfunction has also been linked to cancer and metabolic diseases," the researchers continued
.

After discovering that cancer stem cells might hijack the body clock, Kay and his colleagues then created and tested thousands of molecules that are capable of binding to rogue clock proteins within cancer stem cells and potentially neutralizing them
.

In their newly reported study, the collaborators used some advanced techniques, including artificial intelligence, to determine which molecule is best suited to fight glioblastoma
.

Their newly reported work highlights a particularly promising molecule, known as SHP656, an oral derivative of the molecule KL001, the first synthetic small molecule compound
found to target the CRY protein.

The next step is to test the effectiveness
of SHP656 on actual cancer cells.

Kay said: "We found that this molecule acts differently
on healthy brain cells and tumor cells.

Pharmaceutical companies have now begun Phase I clinical trials
of this new molecule.

SHP656 and other molecules that target clock proteins are expected to treat other types of cancer
in addition to their potential to treat glioblastoma.

The authors conclude: "Our findings suggest that CRY2 plays a direct role in the anti-tumor process of glioblastoma and provides a theoretical basis
for the selective regulation of CRY isomers in the treatment of glioblastoma and other circadian clock-related diseases.

CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy