Gliomas are the most common primary brain tumors and arise from glial cells in the brain. They are a diverse spectrum, from slow-growing to highly aggressive infiltrating tumors. Nearly half of all gliomas are classified as high-grade gliomas (HGG) due to their highly aggressive nature. The standard treatment is surgical removal of the tumor, followed by chemotherapy with temozolomide, radiation therapy, and then nitrosoureas (such as semustine and lomustine). Patient survival has improved moderately over the years, but the prognosis remains poor. There is a median survival of only 5 months without treatment and about 14 months with today’s optimal multimodal treatments. These tumors are typically resistant to existing drugs and often grow back after surgery.
That’s why finding options that are effective and that extend survival is a priority for oncologists. New research has shown that the blood vessels that feed aggressive brain tumors have receptors that could allow a new type of drug-containing nanoparticles to be used to rob tumors of the energy they use to grow and spread, and also cause self- killing by the phenomenon of cellular apoptosis. Scientists from the University of Nottingham and Duke University have found that many of the blood vessels that feed high-grade glioma brain tumors have high levels of low-density lipoprotein receptors (LDLRs). The findings pave the way for the use of drugs already under development at both institutions that could target these receptors and then be taken up by tumors.
The researchers examined microarray biopsies from intra- and inter-tumor regions of 36 adult and 133 pediatric glioblastoma patients to confirm that LDLR is a therapeutic target. Protein expression levels in three representative cell line models were also tested to confirm their utility for testing nanoparticle uptake, retention and cytotoxicity. They showed widespread LDLR expression in the adult and pediatric cohorts, and importantly, they also categorized the observed intra-tumor variation between core and border or invasive regions of adult high-grade gliomas. The researchers will do further tests and possibly a clinical trial to ascertain whether this therapy is feasible and reproducible.
Instead, researchers from the São Paulo Research Foundation (FAPESP) focused on apomorphine, a natural alkaloid that is active against Parkinson’s and the motor alterations that characterize it. Previous research conducted by the group to evaluate the efficacy of 14 of these compounds against squamous cell carcinoma of the head and neck had shown that A5 and C1 were promising and they decided to conduct further investigations. The researchers conducted tests in vitro to evaluate the biological effects of 12 compounds obtained through the total synthesis of apomorphine against glioblastoma cells. They found that two of these compounds, an isoquinoline derivative called A5 and an apomorphine derivative called C1, reduced the viability of glioblastoma cells, suppressed the formation of new cancer stem cells.
These alkaloid derivatives also enhanced the efficacy of temozolomide. If the results of this future research are also promising, he added, it will be possible to move on to clinical trials to confirm the effectiveness of the compounds. Once all these steps are completed, the compounds can finally be used to treat patients with brain cancer.
- By Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific publications
Adekeye AO et al. Pharmaceutics 2023 Feb; 15(29:599.
J Control Release. 2023 Feb; 355:474-488.
Cancer Med. 2023 Feb; 12(4):4270-4281.
Rodrigues-Junior DM et al. Sci Reports 2022; 12(1):21113.
Life Sci. 2022 Nov 15; 309:121023.
– Degree in Medicine and Surgery in 1998 (MD Degree in 1998) – Specialist in Clinical Biochemistry in 2002 (Clinical Biochemistry residency in 2002) – Doctorate in Neurobiology in 2006 (Neurobiology PhD in 2006) – Stayed in the United States, Baltimore (MD ) as a researcher employed by the National Institute on Drug Abuse (NIDA/NIH) and then at Johns Hopkins University, from 2004 to 2008. – Since 2009 he has been involved in Personalized Medicine. – Emergency medical care in private structures since 2010 – Holder of two patents on the preparation of gluten-free products starting from regular enzymatically neutralized wheat flour (owner of patents concerning the production of gluten-free bakery products, starting from regular wheat flour). – Head of the Research and Development department for CoFood srl (Leader of the R&D for the partnership CoFood srl) – Author of articles on medical and health information on the website www.medicomunicare.it (Medical/health information on website) – Author of ECM FAD courses advertised on the website www.salutesicilia.it