Cancer Genes Activated by Common Drugs for Medicament Lobbies Early Diagnosis, Treatment

Research from a team of doctors from Harvard suggests that using the common drugs intended for cancer medicament can activate cancer genes. The doctors said that this can be used to give patients an early diagnosis and treatment.

For people with Myelodysplastic Syndrome (MDS), a group of conditions where there is insufficient production of healthy mature blood cells in the bone marrow,

hypomethylating agents (HMA) are currently used as the first-line treatment. However, the precise way that HMAs function is still a mystery. Even though it hasn't been fully established, they might awaken a dormant oncogene.

In a recent study, scientists from the Harvard Medical School (HMS), Brigham and Women's Hospital (BWH), and National University of Singapore (NUS) Cancer Science Institute of Singapore (CSI Singapore) demonstrated that HMAs can and do activate the oncofetal protein SALL4.

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Cancer-Causing Gene

SALL4 is a recognized oncogene, and it has been discovered that SALL4 expression aids in the growth of leukemia and MDS. Another research team's study from 2016 showed that hypomethylation was linked to SALL4 activation in a liver cancer cell line, and Professor Daniel Tenen from CSI Singapore and his team showed in 2021 that the hepatitis B virus caused SALL4 demethylation in liver cancer through an RNA-mediated mechanism. Professor Tenen's team worked with the other teams to investigate the relationship between HMA use and SALL4 activation, as well as the implications on survival outcomes, to look into potential oncogene upregulation in patients receiving hypomethylating agents.

Before and following their HMA therapy, the research team examined the bone marrow samples of 68 MDS patients. The researchers discovered that HMA therapy could activate the SALL4 oncogene, which would have a negative impact on patient survival, even in cases of complete disease remission.

Tenen stated that their results from this groundbreaking study demonstrate that the hypomethylating agents used in therapy can activate and upregulate cancer genes like SALL4. This implies the necessity of keeping an eye on SALL4 expression levels in patients undergoing HMA therapy. While SALL4 upregulation may likely affect the course of the disease and be linked to a less accurate diagnosis, it may also offer a chance to identify patients for early intervention with a medication that targets SALL4 pathways, improving treatment and patient outcomes.

Nipping the Bud

It's interesting to note that these results from Professor Tenen's team, in collaboration with the BWH and HMS teams, support a study they conducted in 2021 in which they showed that a drug intended to block a SALL4 downstream pathway effectively treated cancer cells with reactivated SALL4 by hypomethylation. The treatment paradigm for other cancers and diseases where HMAs are being used may be changed as a result of these recently established principles.

The team plans to conduct larger prospective studies in the future to confirm these results and create affordable but precise biomarker kits to track SALL4 expression. The team's goal is to create more precise and effective drugs that directly target SALL4 through cross-laboratory collaboration, SciTech Daily reports.

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