Table Info

Table 4.

Mechanisms of action for components of PCV

Medication	Mechanism of action
Procarbazine hydrochloride	Possible mechanism is through the inhibition of trans-methylation of methionine into transfer-RNA (t-RNA) thus inhibiting protein synthesis [25]
Lomustine	Nitrosourea that works as an alkylating agent [9]
Vincristine sulfate	Inhibits the formation of microtubules by binding to tubulin which leads to mitosis arrest. It also is able to block glutamic acid utilization and thereby interfere with the synthesis of nucleic acids and proteins [26]

Declarations

Author contributions

BLW: Conceptualization, Supervision, Writing—review & editing. MM: Conceptualization, Project administration, Visualization. MS, AS and MM: Writing—original draft, Writing—review & editing

Conflicts of interest

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Uniformed Services University of the Health Sciences, the Department of Defense, or the U.S. Government.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

van Solinge TS, Nieland L, Chiocca EA, Broekman MLD. Advances in local therapy for glioblastoma—taking the fight to the tumour. Nat Rev Neurol. 2022;18:221–36. [DOI] [PubMed]

Davis ME. Epidemiology and overview of gliomas. Semin Oncol Nurs. 2018;34:420–9. [DOI] [PubMed]

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23:1231–51. [DOI] [PubMed] [PMC]

Colvin M. Alkylating agents. In: Kufe DW, Pollock RE, Weichselbaum RR, Bast RC Jr, Gansler TS, Holland JF, et al., editors. Holland-Frei cancer medicine. 6th edition. Hamilton (ON): BC Decker; 2003.

Drugs approved for brain tumors [Internet]. National Cancer Institute at the National Institutes of Health; [cited 2023 Oct 7]. Available from: https://www.cancer.gov/about-cancer/treatment/drugs/brain

Wesolowski JR, Rajdev P, Mukherji SK. Temozolomide (temodar). AJNR Am J Neuroradiol. 2010;31:1383–4. [DOI] [PubMed] [PMC]

Xiao ZZ, Wang ZF, Lan T, Huang WH, Zhao YH, Ma C, et al. Carmustine as a supplementary therapeutic option for glioblastoma: a systematic review and meta-analysis. Front Neurol. 2020;11:1036. [DOI] [PubMed] [PMC]

Bartzatt R. Lomustine analogous drug structures for intervention of brain and spinal cord tumors: the benefit of in silico substructure search and analysis. Chemother Res Pract. 2013;2013:360624. [DOI] [PubMed] [PMC]

Weller M, Le Rhun E. How did lomustine become standard of care in recurrent glioblastoma? Cancer Treat Rev. 2020;87:102029. [DOI] [PubMed]

10.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. [DOI] [PubMed]

11.

Chinnaiyan P, Won M, Wen PY, Rojiani AM, Werner-Wasik M, Shih HA, et al. A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913. Neuro Oncol. 2018;20:666–73. [DOI] [PubMed] [PMC]

12.

Lampson LA. Monoclonal antibodies in neuro-oncology: getting past the blood-brain barrier. MAbs. 2011;3:153–60. [DOI] [PubMed] [PMC]

13.

Li Y, Ali S, Clarke J, Cha S. Bevacizumab in recurrent glioma: patterns of treatment failure and implications. Brain Tumor Res Treat. 2017;5:1–9. [DOI] [PubMed] [PMC]

14.

Kazazi-Hyseni F, Beijnen JH, Schellens JH. Bevacizumab. Oncologist. 2010;15:819–25. [DOI] [PubMed] [PMC]

15.

Markham A. Naxitamab: first approval. Drugs. 2021;81:291–6. [DOI] [PubMed]

16.

Furman WL. Monoclonal antibody therapies for high risk neuroblastoma. Biologics. 2021;15:205–19. [DOI] [PubMed] [PMC]

17.

Rubenstein JL, Kim J, Ozawa T, Zhang M, Westphal M, Deen DF, et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia. 2000;2:306–14. [DOI] [PubMed] [PMC]

18.

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–5. [DOI] [PubMed] [PMC]

19.

Castañeda A, Gorostegui M, Miralles SL, Chamizo A, Patiño SC, Flores MA, et al. How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain. ESMO Open. 2022;7:100462. Erratum in: ESMO Open. 2022;7:100504. [DOI] [PubMed] [PMC]

20.

Mora J, Castañeda A, Colombo MC, Gorostegui M, Gomez F, Mañe S, et al. Clinical and pathological evidence of anti-GD2 immunotherapy induced differentiation in relapsed/refractory high-risk neuroblastoma. Cancers (Basel). 2021;13:1264. [DOI] [PubMed] [PMC]

21.

DeWire MD, Fuller C, Campagne O, Lin T, Pan H, Young Poussaint T, et al. A phase I and surgical study of ribociclib and everolimus in children with recurrent or refractory malignant brain tumors: a pediatric brain tumor consortium study. Clin Cancer Res. 2021;27:2442–51. [DOI] [PubMed] [PMC]

22.

Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004;43:83–95. [DOI] [PubMed]

23.

Wang L. Belzutifan approved to treat tumors linked to inherited disorder VHL [Internet]. Source: National Cancer Institute. c2021 [cited 2022 Oct 7]. Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2021/fda-belzutifan-vhl-tumors#:~:text=Belzutifan%20Approved%20to%20Treat%20Tumors%20Linked%20to%20Inherited%20Disorder%20VHL&text=In%20people%20with%20VHL%20disease,inhibits%20HIF%27s%20tumor%2Dpromoting%20activity

24.

Jonasch E, Donskov F, Iliopoulos O, Rathmell WK, Narayan VK, Maughan BL, et al.; MK-6482-004 Investigators. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N Engl J Med. 2021;385:2036–46. [DOI] [PubMed] [PMC]

25.

PubChem compound summary for CID 9703, Procarbazine hydrochloride [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; [cited 2022 Oct 7]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Procarbazine-hydrochloride

26.

Below J, M Das J. Vincristine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019.

27.

Lassman AB. Procarbazine, lomustine and vincristine or temozolomide: which is the better regimen? CNS Oncol. 2015;4:341–6. [DOI] [PubMed] [PMC]

28.

Boyle FM, Eller SL, Grossman SA. Penetration of intra-arterially administered vincristine in experimental brain tumor. Neuro Oncol. 2004;6:300–6. [DOI] [PubMed] [PMC]

29.

Lassman AB, Iwamoto FM, Cloughesy TF, Aldape KD, Rivera AL, Eichler AF, et al. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors. Neuro Oncol. 2011;13:649–59. [DOI] [PubMed] [PMC]

30.

van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, et al. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006;24:2715–22. [DOI] [PubMed]

31.

Thomson RJ, Moshirfar M, Ronquillo Y. Tyrosine kinase inhibitors. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019.

32.

Lombardi G, De Salvo GL, Brandes AA, Eoli M, Rudà R, Faedi M, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019;20:110–19. [DOI] [PubMed]

33.

Lombardi G, Del Bianco P, Brandes AA, Eoli M, Rudà R, Ibrahim T, et al. Patient-reported outcomes in a phase II randomised study of regorafenib compared with lomustine in patients with relapsed glioblastoma (the REGOMA trial). Eur J Cancer. 2021;155:179–90. [DOI] [PubMed]

34.

Durant ST, Zheng L, Wang Y, Chen K, Zhang L, Zhang T, et al. The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv. 2018;4:eaat1719. [DOI] [PubMed] [PMC]

35.

Maggs L, Cattaneo G, Dal AE, Moghaddam AS, Ferrone S. CAR T cell-based immunotherapy for the treatment of glioblastoma. Front Neurosci. 2021;15:662064. [DOI] [PubMed] [PMC]

36.

Lin YJ, Mashouf LA, Lim M. CAR T cell therapy in primary brain tumors: current investigations and the future. Front Immunol. 2022;13:817296. [DOI] [PubMed] [PMC]

37.

Mungur R, Zheng J, Wang B, Chen X, Zhan R, Tong Y. Low-intensity focused ultrasound technique in glioblastoma multiforme treatment. Front Oncol. 2022;12:903059. [DOI] [PubMed] [PMC]

38.

Arsiwala TA, Sprowls SA, Blethen KE, Adkins CE, Saralkar PA, Fladeland RA, et al. Ultrasound-mediated disruption of the blood tumor barrier for improved therapeutic delivery. Neoplasia. 2021;23:676–91. [DOI] [PubMed] [PMC]

39.

Ahmed N, Gandhi D, Melhem ER, Frenkel V. MRI guided focused ultrasound-mediated delivery of therapeutic cells to the brain: a review of the state-of-the-art methodology and future applications. Front Neurol. 2021;12:669449. [DOI] [PubMed] [PMC]