Brain Tumor May Be Targeted Effectively By A Specific Enzyme

Drug resistance can be averted in a subtype of brain tumors by inhibiting a specific enzyme and its regulating factor

Over many years, every other new cancer treatments have faced failure as the tumor cells find ways to become treatment-resistant. Overcoming drug resistance thus sets to be a major goal in cancer research.

Drug resistance developed by a subtype of brain tumors like glioblastomas can be averted as per a study at the Cincinnati Children's Hospital Medical Center, published in the journal Science Advances. The approach may appear beneficial against other cancers, such as melanoma, that also exhibit a similar pathway of drug resistance.

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‘Drug resistance contributes as a key player in cancer treatment. However, the resistance can be averted in a subtype of brain tumors like glioblastomas by inhibiting a specific enzyme – Stearoyl Co-A Desaturase (SCD) and its regulating factor (FOSB). This may help rectify the failures of pre-existing SCD-inhibiting drugs in clinical trials, resulting in a targeted treatment approach. ’

The study team had discovered that certain brain tumors have low amounts of an enzyme called Stearoyl Co-A Desaturase (SCD), which in general is required in elevated levels to fuel the uncontrolled growth of cancer cells. Various drugs, therefore, target SCD to treat tumors.

Silencing of the SCD Pathway

Analysis of publicly available glioblastoma genetic datasets demonstrated that the SCD gene is both deleted as well as its expression suppressed through epigenetic mechanisms in a large subset of glioblastoma patients.

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The incorporation of this concept had the team succeeded by inhibiting this SCD protein and reducing the expression of the transcription factor FOSB (which regulates SCD).

Upon the inhibition of both the protein itself and its regulator, now the tumor cells cannot acquire resistance to the SCD inhibitor, as demonstrated by the longer survival rate of treated (SCD and FOSB inhibition-combination therapy) mice models.

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Furthermore, utilization of Temozolomide (TMZ) – chemotherapeutic agent in advanced tumor models of mice showed relapse in 80%, 50 days post-treatment. Conversely, treatment with TMZ in combination with the SCD inhibitor showed 80% of the mice survival past 50 days.

"This finding was surprising given the requirement of SCD in most cancers," says principal investigator Biplab Dasgupta, PhD, Division of Oncology.

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The research team is yet to explore the survival of glioblastomas that use alternative pathways bypassing SCD.

The findings of present study may serve as a re-assessment tool for SCD-inhibiting drugs in clinical trials. This would help rectify the failures of pre-existing cancer treatments, resulting in targeted efficacies of drugs.

Source-Medindia