Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents
Abstract
1. Introduction
2. Serendipitous Discovery of Conventional Therapies
2.1. Methotrexate
2.2. Vinblastine
2.3. Procarbazine
2.4. Lomustine
2.5. Etoposide
2.6. Avastin
2.7. Temozolomide
3. Out of the Box
3.1. Accutane
3.2. Sildenafil
3.3. Thalidomide
3.4. High-Dose Tamoxifen
3.5. Celebrex
3.6. Gleevec and Hydroxyurea
3.7. Tarceva
3.8. Boswellia
Drug (Year of Discovery) | General Mechanism of Action | Mechanism in Neuro-Oncology |
---|---|---|
Proton Pump Inhibitors (1980) | Blocks the gastric H+/K+-ATPase to decrease acid secretion | May disrupt tumor pH regulation—by inhibiting vacuolar-type H+-ATPases in cancer cells—which can alter drug uptake/resistance and potentially sensitize tumors (e.g., gliomas) [160,161] |
Disulfiram (1881) | Inhibits aldehyde dehydrogenase and modulates cellular redox balance; also affects proteasome and NF-κB signaling | Repurposed to target cancer stem cells (including in glioblastoma) via ALDH inhibition and copper complex formation that increases oxidative stress in tumor cells [162,163] |
Rapamycin (1975) | Binds FKBP12 to inhibit mTOR signaling, thereby reducing cell growth and inducing autophagy | Inhibits mTOR—a pathway often hyperactive in gliomas—to suppress tumor cell proliferation, reduce angiogenesis, and modulate autophagy in brain tumors [164] |
Metformin (1922) | Activates AMP-activated protein kinase (AMPK) to lower hepatic gluconeogenesis and modulate cellular energy metabolism | In neuro-oncology, AMPK activation leads to indirect mTOR inhibition and decreased tumor cell proliferation, with preclinical studies suggesting antiglioma effects [165] |
Lonidamine (1970s) | Inhibits aerobic glycolysis and disrupts mitochondrial energy metabolism in cancer cells | Alters the energy metabolism of tumor cells—including glioma cells—potentially enhancing sensitivity to chemotherapy by targeting the glycolytic pathway [166] |
Chloroquine (1934) | Raises lysosomal pH and blocks autophagy, with additional immunomodulatory actions | By inhibiting autophagy, it can compromise tumor cell survival and may be used to enhance the effects of chemo- and radiotherapy in brain tumors such as glioblastoma [167] |
Chlorpromazine (1950) | Antagonizes dopamine receptors (with additional effects on multiple neurotransmitter systems) | Has been reported to induce apoptosis and interfere with signaling pathways in glioma cells—suggesting potential repurposing as an adjuvant agent in neuro-oncology [168] |
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Aldape, K.; Brindle, K.M.; Chesler, L.; Chopra, R.; Gajjar, A.; Gilbert, M.R.; Gottardo, N.; Gutmann, D.H.; Hargrave, D.; Holland, E.C.; et al. Challenges to curing primary brain tumours. Nat. Rev. Clin. Oncol. 2019, 16, 509–520. [Google Scholar] [CrossRef] [PubMed]
- Mo, F.; Pellerino, A.; Soffietti, R.; Rudà, R. Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance. Int. J. Mol. Sci. 2021, 22, 12654. [Google Scholar] [CrossRef] [PubMed]
- Banks, W.A. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 2009, 9, S3. [Google Scholar] [CrossRef] [PubMed]
- Zhu, L.; Jiang, M.; Wang, H.; Sun, H.; Zhu, J.; Zhao, W.; Fang, Q.; Yu, J.; Chen, P.; Wu, S.; et al. A narrative review of tumor heterogeneity and challenges to tumor drug therapy. Ann. Transl. Med. 2021, 9, 1351. [Google Scholar] [CrossRef]
- Afonso, M.; Brito, M.A. Therapeutic Options in Neuro-Oncology. Int. J. Mol. Sci. 2022, 23, 5351. [Google Scholar] [CrossRef]
- A Note from History: Landmarks in History of Cancer, Part 6—Hajdu-2013-Cancer—Wiley Online Library. Available online: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.28319 (accessed on 26 August 2024).
- Therapeutic Suppression of Tissue Reactivity. 2. Effect of Aminopterin in Rheumatoid Arthritis and Psoriasis. CABI Databases. Available online: https://www.cabidigitallibrary.org/doi/full/10.5555/19511405729 (accessed on 15 September 2024).
- Catala, G.N.; Bestwick, C.S.; Russell, W.R.; Tortora, K.; Giovannelli, L.; Moyer, M.P.; Lendoiro, E.; Duthie, S.J. Folate, genomic stability and colon cancer: The use of single cell gel electrophoresis in assessing the impact of folate in vitro, in vivo and in human biomonitoring. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 2019, 843, 73–80. [Google Scholar] [CrossRef]
- Sobral, A.F.; Cunha, A.; Silva, V.; Gil-Martins, E.; Silva, R.; Barbosa, D.J. Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration. Int. J. Mol. Sci. 2024, 25, 9339. [Google Scholar] [CrossRef]
- Yang, C.; Zhang, J.; Liao, M.; Yang, Y.; Wang, Y.; Yuan, Y.; Ouyang, L. Folate-mediated one-carbon metabolism: A targeting strategy in cancer therapy. Drug Discov. Today 2021, 26, 817–825. [Google Scholar] [CrossRef] [PubMed]
- Farber, S.; Diamond, L.K.; Mercer, R.D.; Sylvester, R.F.; Wolff, J.A. Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyl-Glutamic Acid (Aminopterin). N. Engl. J. Med. 1948, 238, 787–793. [Google Scholar] [CrossRef]
- Discovery—Methotrexate: Chemotherapy Treatment for Cancer—NCI. 30 April 2014. Available online: https://www.cancer.gov/research/progress/discovery/methotrexate (accessed on 15 September 2024).
- Yarris, J.P.; Hunter, A.J. (1909–2002): The cure of choriocarcinoma and its impact on the development of chemotherapy for cancer. Gynecol. Oncol. 2003, 89, 193–198. [Google Scholar] [CrossRef]
- Li, M.C.; Hertz, R.; Spencer, D.B. Effect of Methotrexate Therapy upon Choriocarcinoma and Chorioadenoma. Exp. Biol. Med. 1956, 93, 361–366. [Google Scholar] [CrossRef]
- Chemotherapy of Chorio Carcinoma and Related Trophoblastic Tumors in Women|JAMA|JAMA Network. Available online: https://jamanetwork.com/journals/jama/article-abstract/324744 (accessed on 15 September 2024).
- Schultz, C.; Scott, C.; Sherman, W.; Donahue, B.; Fields, J.; Murray, K.; Fisher, B.; Abrams, R.; Meis-Kindblom, J. Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: Initial report of radiation therapy oncology group protocol 88-06. J. Clin. Oncol. 1996, 14, 556–564. [Google Scholar] [CrossRef] [PubMed]
- Mead, G.M.; Bleehen, N.M.; Gregor, A.; Bullimore, J.; Murrell, D.S.; Rampling, R.P.; Roberts, J.T.; Glaser, M.G.; Lantos, P.; Ironside, J.W.; et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma. Cancer 2000, 89, 1359–1370. [Google Scholar] [CrossRef]
- O’Neill, B.P.; Wang, C.H.; O’Fallon, J.R. Primary central nervous system non-hodgkin’s lymphoma (PCNSL): Survival advantages with combined initial therapy? a final report of the north central cancer treatment group (NCCTG) study 86-72-52. Int. J. Radiat. Oncol. 1999, 43, 559–563. [Google Scholar] [CrossRef]
- Glass, J.; Gruber, M.L.; Cher, L.; Hochberg, F.H. Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: Long-term outcome. J. Neurosurg. 1994, 81, 188–195. [Google Scholar] [CrossRef] [PubMed]
- Abrey, L.E.; DeAngelis, L.M.; Yahalom, J. Long-term survival in primary CNS lymphoma. J. Clin. Oncol. 1998, 16, 859–863. [Google Scholar] [CrossRef] [PubMed]
- De Angelis, L.M.; Yahalom, J.; Thaler, H.T.; Kher, U. Combined modality therapy for primary CNS lymphoma. J. Clin. Oncol. 1992, 10, 635–643. [Google Scholar] [CrossRef]
- Combined Treatment with High-Dose Methotrexate, Vincristine and Procarbazine, Without Intrathecal Chemotherapy, Followed by Consolidation Radiotherapy for Primary Central Nervous System Lymphoma in Immunocompetent Patients|Oncology|Karger Publishers. Available online: https://karger.com/ocl/article-abstract/60/2/134/237089/Combined-Treatment-with-High-Dose-Methotrexate?redirectedFrom=fulltext (accessed on 15 September 2024).
- DeAngelis, L.M.; Seiferheld, W.; Schold, S.C.; Fisher, B.; Schultz, C.J. Combination Chemotherapy and Radiotherapy for Primary Central Nervous System Lymphoma: Radiation Therapy Oncology Group Study 93-10. J. Clin. Oncol. 2002, 20, 4643–4648. [Google Scholar] [CrossRef]
- Abrey, L.E.; Yahalom, J.; DeAngelis, L.M. Treatment for Primary CNS Lymphoma: The Next Step. J. Clin. Oncol. 2000, 18, 3144–3150. [Google Scholar] [CrossRef]
- O’brien, P.; Roos, D.; Pratt, G.; Liew, K.; Barton, M.; Poulsen, M.; Olver, I.; Trotter, G. Phase II Multicenter Study of Brief Single-Agent Methotrexate Followed by Irradiation in Primary CNS Lymphoma. J. Clin. Oncol. 2000, 18, 519. [Google Scholar] [CrossRef]
- Villanueva, G.; Guscott, M.; Schaiquevich, P.; Sampor, C.; Combs, R.; Tentoni, N.; Hwang, M.; Lowe, J.; Howard, S. A Systematic Review of High-Dose Methotrexate for Adults with Primary Central Nervous System Lymphoma. Cancers 2023, 15, 1459. [Google Scholar] [CrossRef] [PubMed]
- Grommes, C.; Rubenstein, J.L.; DeAngelis, L.M.; Ferreri, A.J.M.; Batchelor, T.T. Comprehensive approach to diagnosis and treatment of newly diagnosed primary CNS lymphoma. Neuro-Oncology 2019, 21, 296–305. [Google Scholar] [CrossRef] [PubMed]
- Late Relapse in Primary Central Nervous System lymphoma: Clonal Persistence†|Neuro-Oncology|Oxford Academic. Available online: https://academic.oup.com/neuro-oncology/article/13/5/525/1345176 (accessed on 15 September 2024).
- TJPRC Publication. Vincristine and Vinblastine: A Review. Available online: https://www.academia.edu/23703646/VINCRISTINE_AND_VINBLASTINE_A_REVIEW (accessed on 18 September 2024).
- Wright, J.R. Almost famous: E. Clark Noble, the common thread in the discovery of insulin and vinblastine. CMAJ 2002, 167, 1391–1396. [Google Scholar] [PubMed]
- Duffin, J. Poisoning the Spindle: Serendipity and Discovery of the Anti-Tumor Properties of the Vinca Alkaloids (Part I). Pharm. Hist. 2002, 44, 64–76. [Google Scholar]
- Kruidering-Hall, M.; Katzung, B.G.; Tuan, R.L.; Vanderah, T.W. Cancer Chemotherapy. In Katzung’s Pharmacology Examination & Board Review, 14th ed.; McGraw Hill: New York, NY, USA, 2024. [Google Scholar]
- Vlădutiu, A. Side-Effects of Vinca Alkaloids. Br. Med. J. 1968, 2, 764. [Google Scholar]
- Jongen, J.L.M.; Broijl, A.; Sonneveld, P. Chemotherapy-induced peripheral neuropathies in hematological malignancies. J. Neurooncol. 2015, 121, 229–237. [Google Scholar] [CrossRef]
- Geldof, A.A.; Minneboo, A.; Heimans, J.J. Vinca-alkaloid neurotoxicity measured using an in vitro model. J. Neurooncol. 1998, 37, 109–113. [Google Scholar] [CrossRef]
- PubChem. Procarbazine. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/4915 (accessed on 18 September 2024).
- Sub Laban, T.; Saadabadi, A. Monoamine Oxidase Inhibitors (MAOI). In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK539848/ (accessed on 18 September 2024).
- Holt, A.; Callingham, B.A. The ex vivo effects of procarbazine and methylhydrazine on some rat amine oxidase activities. In Amine Oxidases: Function and Dysfunction; Tipton, K.F., Youdim, M.B.H., Barwell, C.J., Callingham, B.A., Lyles, G.A., Eds.; Springer: Berlin/Heidelberg, Germany, 1994; pp. 439–443. [Google Scholar] [CrossRef]
- Prasad, S.; Gupta, S.C.; Aggarwal, B.B. Serendipity in Cancer Drug Discovery: Rational or Coincidence? Trends Pharmacol. Sci. 2016, 37, 435–450. [Google Scholar] [CrossRef]
- Chu, E. Cancer Chemotherapy. In Katzung’s Basic & Clinical Pharmacology, 16th ed.; Vanderah, T.W., Ed.; McGraw-Hill: New York, NY, USA, 2024; Available online: https://accessmedicine.mhmedical.com/content.aspx?bookid=3382§ionid=281756322 (accessed on 18 September 2024).
- Driessens, N.; Versteyhe, S.; Ghaddhab, C.; Burniat, A.; De Deken, X.; Van Sande, J.; Dumont, J.-E.; Miot, F.; Corvilain, B. Hydrogen peroxide induces DNA single- and double-strand breaks in thyroid cells and is therefore a potential mutagen for this organ. Endocr. Relat. Cancer 2009, 16, 845–856. [Google Scholar] [CrossRef]
- Parasramka, S.; Talari, G.; Villano, J.L.; Rosenfeld, M.; Guo, J. Procarbazine, lomustine and vincristine for recurrent highgrade glioma. Cochrane Database Syst. Rev. 2017, 2017, CD011773. [Google Scholar] [CrossRef]
- Brandes, A.A.; Ermani, M.; Turazzi, S.; Scelzi, E.; Berti, F.; Amistà, P.; Rotilio, A.; Licata, C.; Fiorentino, M.V. Procarbazine and High-Dose Tamoxifen as a Second-Line Regimen in Recurrent High-Grade Gliomas: A Phase II Study. J. Clin. Oncol. 1999, 17, 645. [Google Scholar] [CrossRef]
- Brada, M.; Stenning, S.; Gabe, R.; Thompson, L.C.; Levy, D.; Rampling, R.; Erridge, S.; Saran, F.; Gattamaneni, R.; Hopkins, K.; et al. Temozolomide Versus Procarbazine, Lomustine, and Vincristine in Recurrent High-Grade Glioma. J. Clin. Oncol. 2010, 28, 4601–4608. [Google Scholar] [CrossRef]
- Salem, H.; Sidell, F.R. Blister Agents/Vesicants. In Encyclopedia of Toxicology, 2nd ed.; Wexler, P., Ed.; Elsevier: Amsterdam, The Netherlands, 2005; pp. 319–323. [Google Scholar] [CrossRef]
- Krumbhaar, E.B.; Krumbhaar, H.D. The Blood and Bone Marrow in Yelloe Cross Gas (Mustard Gas) Poisoning. J. Med. Res. 1919, 40, 497–508.3. [Google Scholar] [PubMed]
- Goodman, L.S.; Wintrobe, M.M.; Dameshek, W.; Goodman, M.J.; Gilman, A.; McLennan, M.T. Nitrogen Mustard Therapy: Use of Methyl-Bis(Beta-Chloroethyl)amine Hydrochloride and Tris(Beta-Chloroethyl)amine Hydrochloride for Hodgkin’s Disease, Lymphosarcoma, Leukemia and Certain Allied and Miscellaneous Disorders. JAMA 1984, 251, 2255–2261. [Google Scholar] [CrossRef] [PubMed]
- National Institute of Diabetes and Digestive and Kidney Diseases. Lomustine. In LiverTox: Clinical and Research Information on Drug-Induced Liver Injury; National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, USA, 2012. Available online: http://www.ncbi.nlm.nih.gov/books/NBK548631/ (accessed on 25 August 2024).
- Gerson, S.L.; Caimi, P.F.; William, B.M.; Creger, R.J. Chapter 57—Pharmacology and Molecular Mechanisms of Antineoplastic Agents for Hematologic Malignancies. In Hematology, 7th ed.; Hoffman, R., Benz, E.J., Silberstein, L.E., Weitz, J.I., Salama, M.E., Heslop, H.E., Anastasi, J., Abutalib, S.A., Eds.; Elsevier: Amsterdam, The Netherlands, 2018; pp. 849–912. [Google Scholar] [CrossRef]
- Karadeniz, A.; Alexie, G.; Greten, H.J.; Andersch, K.; Efferth, T. Cytotoxicity of medicinal plants of the West-Canadian Gwich’in Native Americans towards sensitive and multidrug-resistant cancer cells. J. Ethnopharmacol. 2015, 168, 191–200. [Google Scholar] [CrossRef]
- Shah, Z.; Gohar, U.F.; Jamshed, I.; Mushtaq, A.; Mukhtar, H.; Zia-Ui-Haq, M.; Toma, S.I.; Manea, R.; Moga, M.; Popovici, B. Podophyllotoxin: History, Recent Advances and Future Prospects. Biomolecules 2021, 11, 603. [Google Scholar] [CrossRef]
- Gordaliza, M.; García, P.A.; del Corral, J.M.; Castro, M.A.; Gómez-Zurita, M.A. Podophyllotoxin: Distribution, sources, applications and new cytotoxic derivatives. Toxicon 2004, 44, 441–459. [Google Scholar] [CrossRef] [PubMed]
- Jorgsholm, B. Preliminary Experiences with Podophyllin in the Treatment of Skin Carcinomata. Acta Radiol. 1952, 37, 150–161. [Google Scholar] [CrossRef]
- Larsson, L.G. Basal-cell Carcinomas of the Skin Treated by Local Podophyllin Applications: A Preliminary Report. Acta Radiol. 1950, 34, 449–452. [Google Scholar] [CrossRef]
- Montecucco, A.; Zanetta, F.; Biamonti, G. Molecular mechanisms of etoposide. EXCLI J. 2015, 14, 95–108. [Google Scholar]
- Hande, K.R. Etoposide: Four decades of development of a topoisomerase II inhibitor. Eur. J. Cancer 1998, 34, 1514–1521. [Google Scholar] [CrossRef]
- Reyhanoglu, G.; Tadi, P. Etoposide. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK557864/ (accessed on 25 August 2024).
- Carrillo, J.A.; Hsu, F.P.K.; Delashaw, J.; Bota, D. Efficacy and safety of bevacizumab and etoposide combination in patients with recurrent malignant gliomas who have failed bevacizumab. Rev. Health Care 2014, 5, 23–32. [Google Scholar]
- Wei, H.-J.; Upadhyayula, P.S.; Pouliopoulos, A.N.; Englander, Z.K.; Zhang, X.; Jan, C.-I.; Guo, J.; Mela, A.; Zhang, Z.; Wang, T.J.; et al. Focused Ultrasound-Mediated Blood-Brain Barrier Opening Increases Delivery and Efficacy of Etoposide for Glioblastoma Treatment. Int. J. Radiat. Oncol. Biol. Phys. 2021, 110, 539–550. [Google Scholar] [CrossRef] [PubMed]
- Spigelman, M.K.; Zappulla, R.A.; Johnson, J.; Goldsmith, S.J.; Malis, L.I.; Holland, J.F. Etoposide-induced blood-brain barrier disruption. Effect of drug compared with that of solvents. J. Neurosurg. 1984, 61, 674–678. [Google Scholar] [CrossRef] [PubMed]
- Ruggiero, A.; Ariano, A.; Triarico, S.; Capozza, M.A.; Romano, A.; Maurizi, P.; Mastrangelo, S.; Attinà, G. Temozolomide and oral etoposide in children with recurrent malignant brain tumors. Drugs Context 2020, 9, 2020-3-1. [Google Scholar] [CrossRef]
- Bevacizumab—NCI 5 October 2006. Available online: https://www.cancer.gov/about-cancer/treatment/drugs/bevacizumab (accessed on 15 September 2024).
- Ferrara, N.; Leung, D.W.; Cachianes, G.; Winer, J.; Henzel, W.J. Purification and cloning of vascular endothelial growth factor secreted by pituitary folliculostellate cells. Methods Enzymol. 1991, 198, 391–405. [Google Scholar] [CrossRef]
- Ribatti, D. From the discovery of Vascular Endothelial Growth Factor to the introduction of Avastin in clinical trials—An interview with Napoleone Ferrara. Int. J. Dev. Biol. 2011, 55, 383–388. [Google Scholar] [CrossRef]
- de Vries, C.; Escobedo, J.A.; Ueno, H.; Houck, K.; Ferrara, N.; Williams, L.T. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992, 255, 989–991. [Google Scholar] [CrossRef]
- Ferrara, N.; Gerber, H.P.; LeCouter, J. The biology of VEGF and its receptors. Nat. Med. 2003, 9, 669–676. [Google Scholar] [CrossRef]
- LeCouter, J.; Kowalski, J.; Foster, J.; Hass, P.; Zhang, Z.; Dillard-Telm, L.; Frantz, G.; Rangell, L.; DeGuzman, L.; Keller, G.-A.; et al. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 2001, 412, 877–884. [Google Scholar] [CrossRef]
- Gerber, H.P.; Vu, T.H.; Ryan, A.M.; Kowalski, J.; Werb, Z.; Ferrara, N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat. Med. 1999, 5, 623–628. [Google Scholar] [CrossRef] [PubMed]
- LeCouter, J.; Lin, R.; Ferrara, N. Endocrine gland-derived VEGF and the emerging hypothesis of organ-specific regulation of angiogenesis. Nat. Med. 2002, 8, 913–917. [Google Scholar] [CrossRef]
- Ferrara, N.; Chen, H.; Davis-Smyth, T.; Gerber, H.-P.; Nguyen, T.-N.; Peers, D.; Chisholm, V.; Hillan, K.J.; Schwall, R.H. Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat. Med. 1998, 4, 336–340. [Google Scholar] [CrossRef]
- Ferrara, N.; Frantz, G.; LeCouter, J.; Dillard-Telm, L.; Pham, T.; Draksharapu, A.; Giordano, T.; Peale, F. Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am. J. Pathol. 2003, 162, 1881–1893. [Google Scholar] [CrossRef] [PubMed]
- Lammert, E.; Gu, G.; McLaughlin, M.; Brown, D.; Brekken, R.; Murtaugh, L.C.; Gerber, H.-P.; Ferrara, N.; Melton, D.A. Role of VEGF-A in vascularization of pancreatic islets. Curr. Biol. CB 2003, 13, 1070–1074. [Google Scholar] [CrossRef]
- Aiello, L.P.; Avery, R.L.; Arrigg, P.G.; Keyt, B.A.; Jampel, H.D.; Shah, S.T.; Pasquale, L.R.; Thieme, H.; Iwamoto, M.A.; Park, J.E.; et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 1994, 331, 1480–1487. [Google Scholar] [CrossRef]
- Kim, K.J.; Li, B.; Winer, J.; Armanini, M.; Gillett, N.; Phillips, H.S.; Ferrara, N. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993, 362, 841–844. [Google Scholar] [CrossRef]
- Gerber, H.P.; Kowalski, J.; Sherman, D.; Eberhard, D.A.; Ferrara, N. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res. 2000, 60, 6253–6258. [Google Scholar]
- Mesiano, S.; Ferrara, N.; Jaffe, R.B. Role of vascular endothelial growth factor in ovarian cancer: Inhibition of ascites formation by immunoneutralization. Am. J. Pathol. 1998, 153, 1249–1256. [Google Scholar] [CrossRef]
- Borgström, P.; Gold, D.P.; Hillan, K.J.; Ferrara, N. Importance of VEGF for breast cancer angiogenesis in vivo: Implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. 1999, 19, 4203–4214. [Google Scholar]
- Borgström, P.; Bourdon, M.A.; Hillan, K.J.; Sriramarao, P.; Ferrara, N. Neutralizing anti-vascular endothelial growth factor antibody completely inhibits angiogenesis and growth of human prostate carcinoma micro tumors in vivo. Prostate 1998, 35, 1–10. [Google Scholar] [CrossRef]
- Borgström, P.; Hillan, K.J.; Sriramarao, P.; Ferrara, N. Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: Novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res. 1996, 56, 4032–4039. [Google Scholar]
- Warren, R.S.; Yuan, H.; Matli, M.R.; Gillett, N.A.; Ferrara, N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J. Clin. Investig. 1995, 95, 1789–1797. [Google Scholar] [CrossRef]
- Presta, L.G.; Chen, H.; O’Connor, S.J.; Chisholm, V.; Meng, Y.G.; Krummen, L.; Winkler, M.; Ferrara, N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997, 57, 4593–4599. [Google Scholar]
- Yuan, F.; Chen, Y.; Dellian, M.; Safabakhsh, N.; Ferrara, N.; Jain, R.K. Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc. Natl. Acad. Sci. USA 1996, 93, 14765–14770. [Google Scholar] [CrossRef]
- Margolin, K.; Gordon, M.S.; Holmgren, E.; Gaudreault, J.; Novotny, W.; Fyfe, G.; Adelman, D.; Stalter, S.; Breed, J. Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: Pharmacologic and long-term safety data. J. Clin. Oncol. 2001, 19, 851–856. [Google Scholar] [CrossRef]
- Gordon, M.S.; Margolin, K.; Talpaz, M.; Sledge, G.W., Jr.; Holmgren, E.; Benjamin, R.; Stalter, S.; Shak, S.; Adelman, D.C. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J. Clin. Oncol. 2001, 19, 843–850. [Google Scholar] [CrossRef]
- Kabbinavar, F.; Hurwitz, H.I.; Fehrenbacher, L.; Meropol, N.J.; Novotny, W.F.; Lieberman, G.; Griffing, S.; Bergsland, E. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J. Clin. Oncol. 2003, 21, 60–65. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.C.; Haworth, L.; Sherry, R.M.; Hwu, P.; Schwartzentruber, D.J.; Topalian, S.L.; Steinberg, S.M.; Chen, H.X.; Rosenberg, S.A. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med. 2003, 349, 427–434. [Google Scholar] [CrossRef]
- Russo, A.E.; Priolo, D.; Antonelli, G.; Libra, M.; McCubrey, J.A.; Ferraù, F. Bevacizumab in the treatment of NSCLC: Patient selection and perspectives. Lung Cancer Targets Ther. 2017, 8, 259–269. [Google Scholar] [CrossRef]
- Gerstner, E.R.; Sorensen, A.G.; Jain, R.K.; Batchelor, T.T. Anti–Vascular Endothelial Growth Factor Therapy for Malignant Glioma. Curr. Neurol. Neurosci. Rep. 2009, 9, 254–262. [Google Scholar] [CrossRef] [PubMed]
- Flynn, J.R.; Wang, L.; Gillespie, D.L.; Stoddard, G.J.; Reid, J.K.; Owens, J.; Ellsworth, G.B.; Salzman, K.L.; Kinney, A.Y.; Jensen, R.L. Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme. Cancer 2008, 113, 1032–1042. [Google Scholar] [CrossRef]
- Friedman, H.S.; Prados, M.D.; Wen, P.Y.; Mikkelsen, T.; Schiff, D.; Abrey, L.E.; Yung, W.A.; Paleologos, N.; Nicholas, M.K.; Jensen, R.; et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol. 2009, 27, 4733–4740. [Google Scholar] [CrossRef] [PubMed]
- Wick, W.; Gorlia, T.; Taphoorn, M.; Sahm, F.; Harting, I.; Brandes, A.A.; Taal, W.; Domont, J.; Idbaih, A.; Campone, M.; et al. Lomustine and Bevacizumab in Progressive Glioblastoma. N. Engl. J. Med. 2017, 377, 1954–1963. [Google Scholar] [CrossRef] [PubMed]
- Gilbert, M.R.; Dignam, J.J.; Armstrong, T.S.; Wefel, J.S.; Blumenthal, D.T.; Vogelbaum, M.A.; Colman, H.; Chakravarti, A.; Pugh, S.; Won, M.; et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N. Engl. J. Med. 2014, 370, 699–708. [Google Scholar] [CrossRef]
- Ezzati, S.; Salib, S.; Balasubramaniam, M.; Aboud, O. Epidermal Growth Factor Receptor Inhibitors in Glioblastoma: Current Status and Future Possibilities. Int. J. Mol. Sci. 2024, 25, 2316. [Google Scholar] [CrossRef]
- McCrea, H.J.; Ivanidze, J.; O’connor, A.; Hersh, E.H.; Boockvar, J.A.; Gobin, Y.P.; Knopman, J.; Greenfield, J.P. Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: Results of a phase I trial. J. Neurosurg. Pediatr. 2021, 28, 371–379. [Google Scholar] [CrossRef]
- Hasselbalch, B.; Lassen, U.; Hansen, S.; Holmberg, M.; Sorensen, M.; Kosteljanetz, M.; Broholm, H.; Stockhausen, M.-T.; Poulsen, H.S. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: A phase II trial. Neuro-Oncology 2010, 12, 508–516. [Google Scholar] [CrossRef]
- Sathornsumetee, S.; Desjardins, A.; Vredenburgh, J.J.; McLendon, R.E.; Marcello, J.; Herndon, J.E.; Mathe, A.; Hamilton, M.; Rich, J.N.; Norfleet, J.A.; et al. Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro-Oncology 2010, 12, 1300–1310. [Google Scholar] [CrossRef]
- Brain Tumor Trials Collaborative; Raizer, J.J.; Giglio, P.; Hu, J.; Groves, M.; Merrell, R.; Conrad, C.; Phuphanich, S.; Puduvalli, V.K.; Loghin, M.; et al. A phase II study of bevacizumab and erlotinib after radiation and temozolomide in MGMT unmethylated GBM patients. J. Neurooncol. 2016, 126, 185–192. [Google Scholar] [CrossRef]
- Overall Survival in Patients with Glioblastoma Before and After Bevacizumab Approval. Available online: https://www.analysisgroup.com/Insights/publishing/overall-survival-in-patients-with-glioblastoma-before-and-after-bevacizumab-approval/ (accessed on 15 September 2024).
- Johnson, D.R.; Leeper, H.E.; Uhm, J.H. Glioblastoma survival in the United States improved after Food and Drug Administration approval of bevacizumab: A population-based analysis. Cancer 2013, 119, 3489–3495. [Google Scholar] [CrossRef] [PubMed]
- Arney, K. The Story of Temozolomide. Published Online 18 July 2013. Available online: https://news.cancerresearchuk.org/2013/07/18/the-story-of-temozolomide/?utm_source=chatgpt.com (accessed on 25 September 2024).
- Johnson, D.R.; O’Neill, B.P. Glioblastoma survival in the United States before and during the temozolomide era. J. Neurooncol. 2012, 107, 359–364. [Google Scholar] [CrossRef]
- Brandes, A.A. State-of-the-art treatment of high-grade brain tumors. Semin. Oncol. 2003, 30 (Suppl. S19), 4–9. [Google Scholar] [CrossRef]
- Yung, W.K. Temozolomide in malignant gliomas. Semin. Oncol. 2000, 27 (Suppl. S6), 27–34. [Google Scholar] [PubMed]
- Weller, M.; Steinbach, J.P.; Wick, W. Temozolomide: A milestone in the pharmacotherapy of brain tumors. Future Oncol. 2005, 1, 747–754. [Google Scholar] [CrossRef]
- Mohammed, S.; Dinesan, M.; Ajayakumar, T. Survival and quality of life analysis in glioblastoma multiforme with adjuvant chemoradiotherapy: A retrospective study. Rep. Pract. Oncol. Radiother. 2022, 27, 1026–1036. [Google Scholar] [CrossRef]
- Joo, J.D.; Kim, H.; Kim, Y.H.; Han, J.H.; Kim, C.Y. Validation of the Effectiveness and Safety of Temozolomide during and after Radiotherapy for Newly Diagnosed Glioblastomas: 10-year Experience of a Single Institution. J. Korean Med. Sci. 2015, 30, 1597–1603. [Google Scholar] [CrossRef]
- ezierzański, M.; Nafalska, N.; Stopyra, M.; Furgoł, T.; Miciak, M.; Kabut, J.; Gisterek-Grocholska, I. Temozolomide (TMZ) in the Treatment of Glioblastoma Multiforme—A Literature Review and Clinical Outcomes. Curr. Oncol. 2024, 31, 3994–4002. [Google Scholar] [CrossRef]
- Banelli, B.; Carra, E.; Barbieri, F.; Würth, R.; Parodi, F.; Pattarozzi, A.; Carosio, R.; Forlani, A.; Allemanni, G.; Marubbi, D.; et al. The histone demethylase KDM5A is a key factor for the resistance to temozolomide in glioblastoma. Cell Cycle 2015, 14, 3418–3429. [Google Scholar] [CrossRef]
- Kim, G.W.; Lee, D.H.; Yeon, S.-K.; Jeon, Y.H.; Yoo, J.; Lee, S.W.; Kwon, S.H. Temozolomide-resistant Glioblastoma Depends on HDAC6 Activity Through Regulation of DNA Mismatch Repair. Anticancer Res. 2019, 39, 6731–6741. [Google Scholar] [CrossRef]
- Wang, Z.; Hu, P.; Tang, F.; Lian, H.; Chen, X.; Zhang, Y.; He, X.; Liu, W.; Xie, C. HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma. Cancer. Lett. 2016, 379, 134–142. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.Y. Temozolomide resistance in glioblastoma multiforme. Genes Dis. 2016, 3, 198–210. [Google Scholar] [CrossRef]
- Layton, A. The use of isotretinoin in acne. Dermato-endocrinology 2009, 1, 162–169. [Google Scholar] [CrossRef]
- Retinoid Therapy for Neuroblastoma: Historical Overview, Regulatory Challenges, and Prospects—PMC. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854948/ (accessed on 26 August 2024).
- Chandrasekaran, S.; De Sousa, J.F.M.; Paghdar, S.; Khan, T.M.; Patel, N.P.; Tsouklidis, N. Is Isotretinoin in Acne Patients a Psychological Boon or a Bane: A Systematic Review. Cureus 2021, 13, e16834. [Google Scholar] [CrossRef]
- JPM|Free Full-Text|Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions. Available online: https://www.mdpi.com/2075-4426/11/3/211 (accessed on 26 August 2024).
- Sildenafil: From Angina to Erectile Dysfunction to Pulmonary Hypertension Beyond—PMC. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097805/ (accessed on 26 August 2024).
- Haider, M.; Elsherbeny, A.; Pittalà, V.; Fallica, A.N.; Alghamdi, M.A.; Greish, K. The Potential Role of Sildenafil in Cancer Management through EPR Augmentation. J. Pers. Med. 2021, 11, 585. [Google Scholar] [CrossRef] [PubMed]
- Kopanitsa, L.; Kopanitsa, M.V.; Safitri, D.; Ladds, G.; Bailey, D.S. Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition. Int. J. Mol. Sci. 2021, 22, 9665. [Google Scholar] [CrossRef]
- Macháček, M.; Švecová, O.; Bébarová, M. Combination of Sildenafil and Ba2+ at a Low Concentration Show a Significant Synergistic Inhibition of Inward Rectifier Potassium Current Resulting in Action Potential Prolongation. Front. Pharmacol. 2022, 13, 829952. [Google Scholar] [CrossRef]
- Gómez-Vallejo, V.; Ugarte, A.; García-Barroso, C.; Cuadrado-Tejedor, M.; Szczupak, B.; Dopeso-Reyes, I.G.; Lanciego, J.L.; García-Osta, A.; Llop, J.; Oyarzabal, J.; et al. Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels. J. Neurochem. 2016, 136, 403–415. [Google Scholar] [CrossRef] [PubMed]
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma—PMC. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071549/ (accessed on 26 August 2024).
- Andrews, P.L.R.; Williams, R.S.B.; Sanger, G.J. Anti-emetic effects of thalidomide: Evidence, mechanism of action, and future directions. Curr. Res. Pharmacol. Drug Discov. 2022, 3, 100138. [Google Scholar] [CrossRef]
- Lenz, W. Thalidomide and Congenital Abnormalities. In Problems of Birth Defects: From Hippocrates to Thalidomide and After; Persaud, T.V.N., Ed.; Springer: Dordrecht, The Netherlands, 1977; p. 199. [Google Scholar] [CrossRef]
- McBride, W.G. Thalidomide and Congenital Abnormalities. Lancet 1961, 2, 90927–90928. [Google Scholar]
- D’Amato, R.J.; Loughnan, M.S.; Flynn, E.; Folkman, J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. USA 1994, 91, 4082–4085. [Google Scholar] [PubMed]
- Rehman, W.; Arfons, L.M.; Lazarus, H.M. The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development. Ther. Adv. Hematol. 2011, 2, 291–308. [Google Scholar] [CrossRef]
- Fine, H.A.; Figg, W.D.; Jaeckle, K.; Wen, P.Y.; Kyritsis, A.P.; Loeffler, J.S.; Levin, V.A.; Black, P.M.; Kaplan, R.; Pluda, J.M.; et al. Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients with Recurrent High-Grade Gliomas. J. Clin. Oncol. 2000, 18, 4. [Google Scholar]
- Batsaikhan, B.; Wang, J.-Y.; Scerba, M.T.; Tweedie, D.; Greig, N.H.; Miller, J.P.; Hoffer, B.J.; Lin, C.-T.; Wang, J.-Y. Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6′-Dithiothalidomide on Traumatic Brain Injury. Int. J. Mol. Sci. 2019, 20, 502. [Google Scholar] [CrossRef] [PubMed]
- Farrar, M.C.; Jacobs, T.F. Tamoxifen. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK532905/ (accessed on 26 August 2024).
- Yu, F.; Bender, W. The mechanism of tamoxifen in breast cancer prevention. Breast Cancer Res. BCR 2001, 3 (Suppl. S1), A74. [Google Scholar] [CrossRef]
- Lien, E.A.; Wester, K.; Lønning, P.E.; Solheim, E.; Ueland, P.M. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. Br. J. Cancer 1991, 63, 641–645. [Google Scholar] [CrossRef]
- Biomedicines|Free Full-Text|Targeting Protein Kinase C in Glioblastoma Treatment. Available online: https://www.mdpi.com/2227-9059/9/4/381 (accessed on 26 August 2024).
- Robins, H.I.; Won, M.; Seiferheld, W.F.; Schultz, C.J.; Choucair, A.K.; Brachman, D.G.; Demas, W.F.; Mehta, M.P. Phase 2 trial of radiation plus high-dose tamoxifen for glioblastoma multiforme: RTOG protocol BR-0021. Neuro-Oncology 2006, 8, 47–52. [Google Scholar] [CrossRef]
- Saini, S.S.; Gessell-Lee, D.L.; Peterson, J.W. The cox-2-specific inhibitor celecoxib inhibits adenylyl cyclase. Inflammation 2003, 27, 79–88. [Google Scholar] [CrossRef]
- Desai, S.J.; Prickril, B.; Rasooly, A. Mechanisms of phytonutrient modulation of Cyclooxygenase-2 (COX-2) and inflammation related to cancer. Nutr. Cancer 2018, 70, 350–375. [Google Scholar] [CrossRef]
- Saxena, P.; Sharma, P.K.; Purohit, P. A journey of celecoxib from pain to cancer. Prostaglandins Other Lipid Mediat. 2020, 147, 106379. [Google Scholar] [CrossRef]
- Reddy, B.S.; Hirose, Y.; Lubet, R.; Steele, V.; Kelloff, G.; Paulson, S.; Seibert, K.; Rao, C.V. Chemoprevention of colon cancer by specific cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of carcinogenesis. Cancer Res. 2000, 60, 293–297. [Google Scholar]
- Solomon, S.D.; McMurray, J.J.; Pfeffer, M.A.; Wittes, J.; Fowler, R.; Finn, P.; Anderson, W.F.; Zauber, A.; Hawk, E.; Bertagnolli, M. Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention. N. Engl. J. Med. 2005, 352, 1071–1080. [Google Scholar] [CrossRef] [PubMed]
- Kang, K.B.; Zhu, C.; Yong, S.K.; Gao, Q.; Wong, M.C. Enhanced sensitivity of celecoxib in human glioblastoma cells: Induction of DNA damage leading to p53-dependent G1 cell cycle arrest and autophagy. Mol. Cancer. 2009, 8, 66. [Google Scholar] [CrossRef] [PubMed]
- Novakova, I.; Subileau, E.-A.; Toegel, S.; Gruber, D.; Lachmann, B.; Urban, E.; Chesne, C.; Noe, C.R.; Neuhaus, W. Transport Rankings of Non-Steroidal Antiinflammatory Drugs across Blood-Brain Barrier In Vitro Models. PLoS ONE 2014, 9, e86806. [Google Scholar] [CrossRef]
- Yin, D.; Jin, G.; He, H.; Zhou, W.; Fan, Z.; Gong, C.; Zhao, J.; Xiong, H. Celecoxib reverses the glioblastoma chemo-resistance to temozolomide through mitochondrial metabolism. Aging 2021, 13, 21268–21282. [Google Scholar] [CrossRef]
- Flynn, J.P.; Gerriets, V. Imatinib. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK551676/ (accessed on 26 August 2024).
- Iqbal, N.; Iqbal, N. Imatinib: A Breakthrough of Targeted Therapy in Cancer. Chemother. Res. Pract. 2014, 2014, 357027. [Google Scholar] [CrossRef]
- Holdhoff, M.; Supko, J.G.; Gallia, G.L.; Hann, C.L.; Bonekamp, D.; Ye, X.; Cao, B.; Olivi, A.; Grossman, S.A. Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme. J. Neurooncol. 2010, 97, 241–245. [Google Scholar] [CrossRef] [PubMed]
- Yarbro, J.W. Mechanism of action of hydroxyurea. Semin. Oncol. 1992, 19 (Suppl. S9), 1–10. [Google Scholar]
- Hydroxyurea: MedlinePlus Drug Information. Available online: https://medlineplus.gov/druginfo/meds/a682004.html (accessed on 26 August 2024).
- Raymond, E.; Brandes, A.A.; Dittrich, C.; Fumoleau, P.; Coudert, B.; Clement, P.M.; Frenay, M.; Rampling, R.; Stupp, R.; Kros, J.M.; et al. Phase II Study of Imatinib in Patients with Recurrent Gliomas of Various Histologies: A European Organisation for Research and Treatment of Cancer Brain Tumor Group Study. J. Clin. Oncol. 2008, 26, 4659–4665. [Google Scholar] [CrossRef]
- Dresemann, G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: A patient series. Ann. Oncol. 2005, 16, 1702–1708. [Google Scholar] [CrossRef]
- Jinna, S.; Khandhar, P.B. Hydroxyurea Toxicity. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: http://www.ncbi.nlm.nih.gov/books/NBK537209/ (accessed on 26 August 2024).
- Tarceva (Erlotinib) FDA Approval History—Drugs.com. Available online: https://www.drugs.com/history/tarceva.html (accessed on 18 September 2024).
- OSI Pharmaceuticals Announces That Tarceva Has Been Accepted into the FDA’s Pilot 1 Program. Drugs.com. Available online: https://www.drugs.com/nda/tarceva_040629.html (accessed on 18 September 2024).
- Akita, R.W.; Sliwkowski, M.X. Preclinical studies with Erlotinib (Tarceva). Semin. Oncol. 2003, 30 (Suppl. S7), 15–24. [Google Scholar]
- Cohen, M.H.; Johnson, J.R.; Chen, Y.F.; Sridhara, R.; Pazdur, R. FDA Drug Approval Summary: Erlotinib (Tarceva®) Tablets. Oncologist 2005, 10, 461–466. [Google Scholar] [CrossRef] [PubMed]
- Research Yields New Agent for Some Drug-Resistant, Non-Small Cell Lung Cancers. Available online: https://www.dana-farber.org/newsroom/news-releases/2009/research-yields-new-agent-for-some-drug-resistant-non-small-cell-lung-cancers (accessed on 18 September 2024).
- de Groot, J.F.; Gilbert, M.R.; Aldape, K.; Hess, K.R.; Hanna, T.A.; Ictech, S.; Groves, M.D.; Conrad, C.; Colman, H.; Puduvalli, V.K.; et al. Phase II study of carboplatin and erlotinib (Tarceva, OSI-774) in patients with recurrent glioblastoma. J. Neurooncol. 2008, 90, 89–97. [Google Scholar] [CrossRef] [PubMed]
- Wen, P.Y.; Chang, S.M.; Lamborn, K.R.; Kuhn, J.G.; Norden, A.D.; Cloughesy, T.F.; Robins, H.I.; Lieberman, F.S.; Gilbert, M.R.; Mehta, M.P.; et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro-Oncology 2014, 16, 567–578. [Google Scholar] [CrossRef]
- Trivedi, V.L.; Soni, R.; Dhyani, P.; Sati, P.; Tejada, S.; Sureda, A.; Setzer, W.N.; Razis, A.F.A.; Modu, B.; Butnariu, M.; et al. Anti-cancer properties of boswellic acids: Mechanism of action as anti-cancerous agent. Front. Pharmacol. 2023, 14, 1187181. [Google Scholar] [CrossRef]
- Qurishi, Y.; Hamid, A.; Sharma, P.R.; Wani, Z.A.; Mondhe, D.M.; Singh, S.K.; Zargar, M.A.; Andotra, S.S.; Shah, B.A.; Taneja, S.C.; et al. PARP Cleavage and Perturbance in Mitochondrial Membrane Potential by 3-α-Propionyloxy-β-Boswellic Acid Results in Cancer Cell Death and Tumor Regression in Murine Models. Future Oncol. 2012, 8, 867–881. [Google Scholar] [CrossRef] [PubMed]
- Boswellic Acids and Malignant Glioma: Induction of Apoptosis but No Modulation of Drug Sensitivity—PubMed. Available online: https://pubmed.ncbi.nlm.nih.gov/10360653/ (accessed on 26 August 2024).
- Sawaid, I.O.; Samson, A.O. Proton Pump Inhibitors and Cancer Risk: A Comprehensive Review of Epidemiological and Mechanistic Evidence. J. Clin. Med. 2024, 13, 1970. [Google Scholar] [CrossRef]
- Bridoux, M.; Simon, N.; Turpin, A. Proton Pump Inhibitors and Cancer: Current State of Play. Front. Pharmacol. 2022, 13, 798272. [Google Scholar] [CrossRef]
- PubChem. Disulfiram. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/3117 (accessed on 24 February 2025).
- Hothi, P.; Martins, T.J.; Chen, L.; Deleyrolle, L.; Yoon, J.-G.; Reynolds, B.; Foltz, G. High-Throughput Chemical Screens Identify Disulfiram as an Inhibitor of Human Glioblastoma Stem Cells. Oncotarget 2012, 3, 1124–1136. [Google Scholar] [CrossRef]
- PubChem. Sirolimus. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/5284616 (accessed on 24 February 2025).
- PubChem. Metformin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/4091 (accessed on 24 February 2025).
- PubChem. Lonidamine. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/39562 (accessed on 24 February 2025).
- PubChem. Chloroquine. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/2719 (accessed on 24 February 2025).
- PubChem. Chlorpromazine. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/2726 (accessed on 24 February 2025).
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Nadora, D.; Ezzati, S.; Bol, B.; Aboud, O. Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents. Int. J. Mol. Sci. 2025, 26, 2955. https://doi.org/10.3390/ijms26072955
Nadora D, Ezzati S, Bol B, Aboud O. Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents. International Journal of Molecular Sciences. 2025; 26(7):2955. https://doi.org/10.3390/ijms26072955
Chicago/Turabian StyleNadora, Denise, Shawyon Ezzati, Brandon Bol, and Orwa Aboud. 2025. "Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents" International Journal of Molecular Sciences 26, no. 7: 2955. https://doi.org/10.3390/ijms26072955
APA StyleNadora, D., Ezzati, S., Bol, B., & Aboud, O. (2025). Serendipity in Neuro-Oncology: The Evolution of Chemotherapeutic Agents. International Journal of Molecular Sciences, 26(7), 2955. https://doi.org/10.3390/ijms26072955