Optimal Treatment Timing Could Boost Cancer Therapy Efficacy

Administering chemotherapy at specific times could significantly improve outcomes for brain cancer patients. Washington University in St. Louis researchers discovered that treatment timing plays a crucial role in how effectively glioblastoma patients respond to standard drug protocols. Funding came from NCI, Siteman Cancer Center, and National Institutes of Health, with the cancer center operating at WashU Medicine and Barnes-Jewish Hospital. 

Examining glioblastoma’s resistance to treatment despite affecting hundreds of thousands annually, the findings were published in the Journal of Neuro-Oncology. While Temozolomide remains the go-to chemotherapy compound for this malignancy, many patients see limited benefits. Cancer cells typically activate MGMT, a repair enzyme that neutralizes the medication’s DNA-damaging effects, enabling tumors to survive treatments like Temozolomide that should destroy them. 

Researchers found that this enzyme’s activity levels shift throughout each 24-hour period rather than remaining constant. Both the gene’s methylation status, which shuts it down, and protein quantities fluctuate with biological rhythms. This discovery prompted investigators to examine whether sample collection timing affects diagnostic outcomes. 

Analysis by Herzog and colleagues covered patient biopsy information spanning five years provided by Omar Butt, Will Leidig, and Joshua Rubin from the WashU Medicine team. Rubin noted that methylation serves diagnostic functions in cancer care currently, particularly for categorizing brain tumor molecular variants that correspond with differing treatment responses. 

Investigation results showed methylation levels don’t remain steady but shift during different hours. Morning samples demonstrated greater probability of methylation detection repeatedly, the team observed. Collecting tissue samples at varying hours could therefore alter tumor diagnosis. Optimism exists that this time-based diagnostic method will uncover improved treatment approaches for this devastating illness. 

Daily cycles in the MGMT gene and protein output also control how tumors respond to temozolomide across each day. The researchers discovered that morning administration proves more effective, suggesting that this aligns with periods when less enzyme is available for repairing drug-induced cellular damage. 

Graduate student Maria Gonzalez-Aponte from the research group tracked enzyme levels across daily cycles in tumor cells and patient tissue. Collaborating with mathematical biologist Olivia Walch, they constructed a computational model forecasting when temozolomide would achieve maximum impact relative to enzyme fluctuations. 

Walch explained that mathematics enables insights beyond what intuition alone reveals. Because temozolomide needs multiple hours to generate DNA damage and trigger programmed cell death, the model indicated that administering it shortly after enzyme protein crests provides the medication its best opportunity to act while cellular repair systems operate at reduced capacity. 

While time-based medicine appears straightforward conceptually, identifying optimal dosing windows still presents substantial challenges. 

As more teams at firms like CNS Pharmaceuticals Inc. (NASDAQ: CNSP) undertake R&D programs aimed at developing novel therapies against brain cancers, more insights about these malignancies are likely to be uncovered and pave the way for new approaches to treating these conditions. 

NOTE TO INVESTORS: The latest news and updates relating to CNS Pharmaceuticals Inc. (NASDAQ: CNSP) are available in the company’s newsroom at https://ibn.fm/CNSP 

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