Husain Yar Khan

Khuloud Bajbouj

Mai F. Tolba

Frontiers in Pharmacology

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Editorial: Emerging talents inpharmacology of anti-cancerdrugs 2022Husain Yar Khan1, Khuloud Bajbouj2,3 and Mai F. Tolba4,5*1Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, United States,2College of Medicine, University of Sharjah, Sharjah, United Arab Emirates, 3Research Institute for MedicalandHealth Sciences, University of Sharjah, Sharjah, United Arab Emirates, 4CNIO-Spanish National CancerResearch Center, Melchor Fernandez Almagro, Madrid, Spain, 5Department of Pharmacology andToxicology, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptKEYWORDSbreast cancer, hepatocellular carcinoma, colon cancer, pancreatic cancer, lung cancerEditorial on the Research TopicEmerging talents in pharmacology of anti-cancer drugs 2022Continuous research efforts have significantly unraveled fundamental molecular pathwaysthat have contributed to paving the way for the development of a multitude of therapeuticstrategies, which have and expanded the arsenal of weapons against cancer. This has beentremendously reflected on the uplifting of the cancer survival curve and the improvement of thequality of life of cancer patients. The Research Topic herein was dedicated to highlighting theemerging talents of student researchers pursuing studies in the area of pharmacology of anticancerdrugs. The articles in this Research Topic have shed light on the quality and diversity of studentresearchers across this field and focused on threemain themes: 1) Remodeling Cancer Epigenome:Therapeutic Advances; 2) Cancer Immunosurveillance: From Mechanisms to Therapy; 3)Anticancer Drug Discovery and Translational Oncology. The studies herein include tworeports of clinical trials by Tan et al. and Zhu et al. A diversity of preclinical/translationalresearch studies were also presented in the Research Topic. Lozon et al. presented a novelchemotherapy combination that was validated in vitro in colon cancer and lung cancer cell lines.Abdollah et al., Yang et al., and Lee et al. highlighted a promising anticancer activity for a variety ofnatural products against hepatocellular carcinoma. On the other hand, the work of Lee et al., Linet al., Irshad et al., and Kuttikrishnan et al. presented mechanistic insights in pancreatic cancer,breast cancer, non-small-cell lung cancer, and leukemia. TheResearchTopic also encompasses twoliterature reviews by Bannoura et al. and Yuan et al.Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate, has shown antitumor activityin patients with HER2-low advanced breast cancer (ABC) in clinical trials. However, the cost-effectiveness of T-DXdwas not clearly established. In order to determinewhether the benefits of thistreatment outweigh its costs, Zhu et al. employed aMarkov decision-analyticmodel to compare thecost-effectiveness of T-DXdwith chemotherapy inHER2-lowABC patients.While T-DXd showedimproved quality-adjusted life years (QALYs), its incorporation led to increased costs and anunfavorable incremental cost-effectiveness ratio (ICER) compared to chemotherapy, making itdevoid of cost-effectiveness in HER2-low ABC patients in the United States. The authors, however,believe that it may still provide health benefits to patients with HR+/HER2-low ABC.In their case report, Tan et al. suggested that pembrolizumab plus nab-paclitaxel mightbe a potential treatment option for patients with cholangiocarcinoma (CCA), which is aOPEN ACCESSEDITED AND REVIEWED BYOlivier Feron,Université catholique de Louvain,Belgium*CORRESPONDENCEMai F. Tolba,tolba.mf@pharma.asu.edu.egSPECIALTY SECTIONThis article was submitted toPharmacology of Anti-Cancer Drugs, asection of the journalFrontiers in PharmacologyRECEIVED 21 March 2023ACCEPTED 27 March 2023PUBLISHED 19 April 2023CITATIONKhan HY, Bajbouj K and Tolba MF (2023),Editorial: Emerging talents inpharmacology of anti-cancerdrugs 2022.Front. Pharmacol. 14:1191321.doi: 10.3389/fphar.2023.1191321COPYRIGHT© 2023 Khan, Bajbouj and Tolba. This isan open-access article distributed underthe terms of the Creative CommonsAttribution License (CC BY). The use,distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publicationin this journal is cited, in accordance withaccepted academic practice. No use,distribution or reproduction is permittedwhich does not comply with these terms.Frontiers in Pharmacology frontiersin.org01TYPE EditorialPUBLISHED 19 April 2023DOI 10.3389/fphar.2023.1191321highly aggressive malignancy with poor overall survival. In thisreport, a metastatic extrahepatic CCA patient achieved durableresponse and good tolerance to a combination treatment ofpembrolizumab plus nab-paclitaxel following progression on achemotherapy of gemcitabine and capecitabine.Lozon et al. contributed an original article highlighting theimportance of safranal (SAF) as a promising candidate-sensitizingagent of human colon cancer cells (HCT116) and lung cancer cells(A549) to the cytotoxic effect of the topoisomerase inhibitor topotecan(TPT). The combination augmented TPT-induced alterations in DNArepair and boosted the incidence of double-strand breaks withsubsequent induction of apoptosis. The sensitization only occurredwhen the cells were pretreated with SAF 24 h before TPT treatment.However, simultaneous exposure or adding SAF 24 h after TPT did notrecapitulate the same results. Hence, the effect was sequence dependent.An article by Abdollah et al. aimed to determine whether fucoidan’schemomodulatory benefits may be enhanced by using it in combinationwith the FDA-approved antiangiogenic drugs sorafenib and Avastin(bevacizumab) in order to augment their anticancer activity inhepatocellular carcinoma (HCC) cells. The authors reported that thecombination treatment inhibited the PI3K/AKT/mTOR and KRAS/BRAF/MAPK pathways in addition to apoptosis induction inHCC bothin vitro and in vivo.Yang et al. identified a potential pharmacological mechanism bywhich Ganji Fang (GJF) can treat HCC at the systemic level. Theunderlying mechanisms were shown to involve immune control, cellmigration, cell proliferation, apoptosis, and inflammation induction.Furthermore, it was demonstrated that the G0/G1 phase cycle arrestsubsequent to the apoptosis after GJF treatment in liver cancer cellswas triggered by blocking the PI3K/Akt signaling pathway.Pachymic acid has been shown to be the significant activecomponent of GJF that exhibits anticancer action, andEPHA2 may be a potential key target for GJF in HCC.It was previously found that white genius mushroom (WGM), apopular edible mushroom in Taiwan, mediates strong antiproliferativeactivities against human Hep3B liver cancer cells. However, theunderlying mechanisms have not been fully investigated. Lee et al.reported that WGM extracts induced cell death by targeting mTORand MAPK signaling pathways in liver cancer cells, suggesting that theycould be used as a pharmacologically safe natural dietarychemopreventive agent for HCC treatment.The article by Lee et al. investigated the efficacy and molecularmechanisms of ivermectin/gemcitabine combination in pancreaticcancer. They observed that a combination treatment of ivermectinand gemcitabine suppressed pancreatic cancer both in vitro and invivo more effectively than gemcitabine alone. Mechanistically, thiscombination was found to exert its effects by inhibiting cellproliferation via G1 cell cycle arrest and augmenting apoptosis byinducing mitochondrial dysfunction. Based on these findings, thestudy concluded that ivermectin, an antiparasitic drug, can exhibitsynergistic effects with gemcitabine and may be repurposed to serveas a promising therapeutic agent for pancreatic cancer therapy.Lin et al. demonstrated the anticancer effects of gallic acid, a phenolicacid known for its antioxidant properties, against triple-negative breastcancer cells in vitro. The study showed that gallic acid was able to inhibitthe growth of HCC1806 cells and stimulate their apoptosis by triggeringthe production of reactive oxygen species, which modulate the PI3K/AKT/EGFR and MAPK signaling pathways.Irshad et al. employed integrative network pharmacology, moleculardocking, and in vitro experiments to elucidate the mechanism of actionof glycyrrhetinic acid (18α-GA), a triterpenoid found in licorice againstnon-small-cell lung cancer (NSCLC). Their network pharmacologystudy identified EGFR, AKT1, PI3KR1, MAPK1, IGF1, and SRC ascrucial hub targets for 18α-GA against NSCLC. The authors furthershowed that 18α-GA augmentedG1 cell cycle arrest, triggered apoptosis,reduced the migratory potential, and inhibited the EGFR-PI3K/AKTpathway in NSCLC cell lines.Kuttikrishnan et al. explored the role of neosetophomone-B (NSP-B), a meroterpenoid fungal secondary metabolite, on the FOXM1/BUB1B signaling pathway. The development and progression ofvarious types of cancer, including chronic myelogenous leukemia,have been linked to the abnormal expression of FOXM1 and BUB1Bgenes. A TCGA data analysis elaborated that BUB1B is overexpressed inmost cancers and linked with poor prognosis. Using gene expressionprofiling, the authors showed the significant downregulation of BUB1Bin leukemia cells treated with NSP-B. In addition, they validated their insilico findings in vitro by showing that NSP-B suppresses the expressionof FOXM1 and BUB1B in a dose-dependent manner, leading tocompromised cell viability and apoptosis induction in leukemia cells.The minireview by Bannoura et al. summarized the recent data ontargeting KRAS G12D, which is among the most common mutations(45%) in pancreatic cancer that are associated with poor prognosis. Thearticle discussed several modalities under development for targetingKRAS G12D, including small molecule inhibitors and immunotherapy.Yuan et al. contributed a bibliometric article of the literaturefrom the Web of Science Core Research Topic (2002–2021) on theemerging trends and research foci of the natural compoundberberine in cancer. Berberine is a multitarget Chinese medicinemonomer compound that is extensively studied for its antitumor/antiproliferative effects and its capacity to sensitize cancer cells tochemotherapy. The collected data showed that berberine exhibitsanticancer capacity through a diversity of mechanisms, includinghalting the cell cycle, inhibition of tumor cell invasion andmigration, and inducing autophagy and apoptotic cell death.Author contributionsAll authors listed havemade a substantial, direct, and intellectualcontribution to the work and approved it for publication.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of the authors anddo not necessarily represent those of their affiliated organizations, orthose of the publisher, the editors and the reviewers. Any product thatmay be evaluated in this article, or claim that may be made by itsmanufacturer, is not guaranteed or endorsed by the publisher.Frontiers in Pharmacology frontiersin.org02Khan et al. 10.3389/fphar.2023.1191321

Editorial: Emerging talents in pharmacology of anti-cancer drugs 2022

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Editorial: Emerging talents in pharmacology of anti-cancer drugs 2022

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