Wetenschappers selecteren 38 geneesmiddelen die effectief bleken bij andere vormen van kanker die effectief zouden kunnen zijn bij baarmoederhalskanker

Raadpleeg ook literatuurlijst niet-toxische middelen en behandelingen specifiek bij baarmoederhalskanker en baarmoederkanker van arts-bioloog drs. Engelbert Valstar.

22 november 2022: Bron: International Journal of Gynecological Cancer (BMJ)

Onderzoekers van het Antikankerfonds, het Tata Memorial Centre (India) en het Erasmus MC Kanker Instituut (Nederland) hebben een lijst samengesteld van 38 geneesmiddelen die een mogelijke effectieve behandeling zouden kunnen zijn bij baarmoederhalskanker. De 38 potentiële medicijnen kwamen uit een uitgebreid literatuuronderzoek onder ruim 500 medicijnen die bij andere vormen van kanker en ziektes effectieve resultaten hebben laten zien en op basis van samenstelling en lopende studies wellicht ook een effectieve behandeling zouden kunnen zijn voor patiënten met baarmoederhalskanker.

Een op literatuur gebaseerde benadering werd uitgevoerd om mogelijkheden voor herbestemming van geneesmiddelen bij baarmoederhalskanker te identificeren om toekomstig onderzoek en studies op te zetten. Herbestemming van geneesmiddelen is een alternatieve ontwikkelingsroute die gebruikmaakt van de eigenschappen van geneesmiddelen die zijn goedgekeurd voor andere ziekten en voortbouwt op beschikbare veiligheids- en farmacologische gegevens om het geneesmiddel te ontwikkelen als een mogelijke behandeling voor andere ziekten.

Van de 534 geneesmiddelen die werden geanalyseerd hadden er 174 (33%) ten minste één relevante abstracte of geregistreerde studie bij baarmoederhalskanker. Van 94 (18%) medicijnen waren ten minste onderzoek van menselijke gegevens beschikbaar en 52 (10%) medicijnen werden geëvalueerd in geregistreerde onderzoeken.

Om prioriteit te geven aan geneesmiddelen die in aanmerking komen voor toekomstig onderzoek, werden alle 174 geneesmiddelen verder beoordeeld op de sterkte van de wetenschappelijke onderbouwing, de haalbaarheid van integratie in de standaardzorg voor baarmoederhalskanker, het bewijs van radiotherapie gevoeligheid en het mogelijke werkingsmechanisme. Van de 174 geneesmiddelen werden uiteindelijk 38 (22%) potentiële kandidaat-geneesmiddelen geselecteerd.

Deze studie is gepubliceerd in het International Journal of Gynecological Cancer (BMJ) en gratis in te zien of te downloaden. Klik op de titel van het abstract voor het volledige studieverslag.

Original research

Drug repurposing as a potential source of innovative therapies in cervical cancer

http://orcid.org/0000-0003-2859-5192

Rica Capistrano I.1,
Sonz Paul2,
Ingrid Boere3,
Pan Pantziarka1,4,
Supriya Chopra5,
Remi A Nout3 and
Gauthier Bouche1

Correspondence to Dr Rica Capistrano I., Anticancer Fund, Meise, Belgium; rica.capistrano@anticancerfund.org

Abstract

Objective Drug repurposing is an alternative development pathway that utilizes the properties of drugs approved for other diseases and builds on available safety and pharmacological data to develop the drug as a potential treatment for other diseases. A literature-based approach was performed to identify drug repurposing opportunities in cervical cancer to inform future research and trials.

Methods We queried PubMed for each drug included in two databases (ReDO_DB and CDcervix_DB, which include 300+ non-cancer drugs and 200+ cancer drugs not used in cervical cancer, respectively) and manually assessed all abstracts for relevance and activity in cervix cancer, and type of evidence. Subsequently, we also performed a search of clinical trial databases where we generated a list of registered trials in cervical cancer with all drugs from our databases.

Results Of the 534 drugs from both databases, 174 (33%) had at least one relevant abstract or registered trial in cervical cancer. 94 (18%) drugs had at least human data available, and 52 (10%) drugs were evaluated in registered trials. To prioritize drugs to consider for future trials, all 174 drugs were further assessed for strength of scientific rationale, feasibility for integration in cervical cancer standard of care, evidence of radiosensitization, and potential mechanism of action. Out of the 174 drugs, 38 (22%) potential drug candidates were selected.

Conclusion This study resulted in a list of candidate drugs for potential evaluation in cervical cancer. Many drugs might warrant additional (pre)clinical investigation, which could be done in a coordinated manner using platform trials.

Data availability statement

Data are available in a public, open access repository.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Data availability statement

Data are available in a public, open access repository.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

References

↵
1. Bray F,
2. Ferlay J,
3. Soerjomataram I, et al
. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.doi:10.3322/caac.21492pmid:http://www.ncbi.nlm.nih.gov/pubmed/30207593
CrossRef PubMed Google Scholar
↵
1. Rose PG,
2. Bundy BN,
3. Watkins EB, et al
. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999;340:1144–53.doi:10.1056/NEJM199904153401502pmid:http://www.ncbi.nlm.nih.gov/pubmed/10202165
CrossRef PubMed Web of Science Google Scholar
↵
1. Gupta S,
2. Maheshwari A,
3. Parab P, et al
. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIb squamous cervical cancer: a randomized controlled trial. J Clin Oncol 2018;36:1548–55.doi:10.1200/JCO.2017.75.9985pmid:http://www.ncbi.nlm.nih.gov/pubmed/29432076
CrossRef PubMed Google Scholar
↵
1. Kenter G,
2. Greggi S,
3. Vergote I, et al
. Results from neoadjuvant chemotherapy followed by surgery compared to chemoradiation for stage IB2-IIB cervical cancer, EORTC 55994. JCO 2019;37:5503.doi:10.1200/JCO.2019.37.15_suppl.5503
Google Scholar
↵
1. Horeweg N,
2. Mittal P,
3. Gradowska PL, et al
. Adjuvant systemic therapy after chemoradiation and brachytherapy for locally advanced cervical cancer: a systematic review and meta-analysis. Cancers 2021;13:13.doi:10.3390/cancers13081880pmid:http://www.ncbi.nlm.nih.gov/pubmed/33919905
PubMed Google Scholar
↵
1. Mileshkin LR,
2. Moore KN,
3. Barnes E, et al
. Adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: the randomized phase III OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274). JCO 2021;39:LBA3.doi:10.1200/JCO.2021.39.15_suppl.LBA3
Google Scholar
↵
1. Tewari KS,
2. Sill MW,
3. Long HJ, et al
. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734–43.doi:10.1056/NEJMoa1309748pmid:http://www.ncbi.nlm.nih.gov/pubmed/24552320
CrossRef PubMed Google Scholar
↵
1. Colombo N,
2. Dubot C,
3. Lorusso D, et al
. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med 2021;385:1856–67.doi:10.1056/NEJMoa2112435pmid:http://www.ncbi.nlm.nih.gov/pubmed/34534429
PubMed Google Scholar
↵
1. Tewari KS,
2. Monk BJ,
3. Vergote I, et al
. Survival with cemiplimab in recurrent cervical cancer. N Engl J Med 2022;386:544–55.doi:10.1056/NEJMoa2112187pmid:http://www.ncbi.nlm.nih.gov/pubmed/35139273
PubMed Google Scholar
↵
1. Naumann RW,
2. Oaknin A,
3. Meyer T, et al
. Efficacy and safety of nivolumab (Nivo) + ipilimumab (IPI) in patients (PTS) with recurrent/metastatic (r/m) cervical cancer: results from CheckMate 358. Ann Oncol 2019;30:v898–9.doi:10.1093/annonc/mdz394.059
Google Scholar
↵
1. Coleman RL,
2. Lorusso D,
3. Gennigens C, et al
. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2021;22:609–19.doi:10.1016/S1470-2045(21)00056-5pmid:http://www.ncbi.nlm.nih.gov/pubmed/33845034
PubMed Google Scholar
↵
1. Pushpakom S,
2. Iorio F,
3. Eyers PA, et al
. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019;18:41–58.doi:10.1038/nrd.2018.168pmid:http://www.ncbi.nlm.nih.gov/pubmed/30310233
CrossRef PubMed Google Scholar
↵
1. Bertolini F,
2. Sukhatme VP,
3. Bouche G
. Drug repurposing in oncology--patient and health systems opportunities. Nat Rev Clin Oncol 2015;12:732–42.doi:10.1038/nrclinonc.2015.169pmid:http://www.ncbi.nlm.nih.gov/pubmed/26483297
CrossRef PubMed Google Scholar
↵
1. Pantziarka P,
2. Verbaanderd C,
3. Sukhatme V, et al
. ReDO_DB: the repurposing drugs in oncology database. Ecancermedicalscience 2018;12:886.doi:10.3332/ecancer.2018.886pmid:http://www.ncbi.nlm.nih.gov/pubmed/30679953
PubMed Google Scholar
↵
1. Pantziarka P,
2. Capistrano I R,
3. De Potter A, et al
. An open access database of licensed cancer drugs. Front Pharmacol 2021;12:627574.doi:10.3389/fphar.2021.627574pmid:http://www.ncbi.nlm.nih.gov/pubmed/33776770
PubMed Google Scholar
↵
1. Pantziarka P,
2. Verbaanderd C,
3. Huys I, et al
. Repurposing drugs in oncology: from candidate selection to clinical adoption. Semin Cancer Biol 2021;68:186–91.doi:10.1016/j.semcancer.2020.01.008pmid:http://www.ncbi.nlm.nih.gov/pubmed/31982510
PubMed Google Scholar
↵
1. Lin LL,
2. Lakomy DS,
3. Ning MS, et al
. Combining novel agents with radiotherapy for gynecologic malignancies: beyond the era of cisplatin. Int J Gynecol Cancer 2020;30:409–23.doi:10.1136/ijgc-2020-001227pmid:http://www.ncbi.nlm.nih.gov/pubmed/32193219
Abstract/FREE Full Text Google Scholar
↵
1. Chaudary N,
2. Pintilie M,
3. Hedley D, et al
. Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic cervical cancer xenografts. Br J Cancer 2017;116:50–7.doi:10.1038/bjc.2016.383pmid:http://www.ncbi.nlm.nih.gov/pubmed/27875522
PubMed Google Scholar
↵
1. Garcia-Soto AE,
2. McKenzie ND,
3. Whicker ME, et al
. Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer. Cancer 2021;127:2279–93.doi:10.1002/cncr.33449pmid:http://www.ncbi.nlm.nih.gov/pubmed/33932031
PubMed Google Scholar
↵
1. Bianchi A,
2. Lopez S,
3. Altwerger G, et al
. PARP-1 activity (PAR) determines the sensitivity of cervical cancer to olaparib. Gynecol Oncol 2019;155:144–50.doi:10.1016/j.ygyno.2019.08.010pmid:http://www.ncbi.nlm.nih.gov/pubmed/31434613
PubMed Google Scholar
↵
1. Tang M,
2. Liu Q,
3. Zhou L, et al
. The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer. Invest New Drugs 2019;37:65–75.doi:10.1007/s10637-018-0616-7pmid:http://www.ncbi.nlm.nih.gov/pubmed/29872938
PubMed Google Scholar
↵
1. Jiao X,
2. Nawab O,
3. Patel T, et al
. Recent advances targeting CCR5 for cancer and its role in immuno-oncology. Cancer Res 2019;79:4801–7.doi:10.1158/0008-5472.CAN-19-1167pmid:http://www.ncbi.nlm.nih.gov/pubmed/31292161
Abstract/FREE Full Text Google Scholar
↵
1. Tormoen GW,
2. Blair TC,
3. Bambina S, et al
. Targeting MERTK enhances adaptive immune responses after radiation therapy. Int J Radiat Oncol Biol Phys 2020;108:93–103.doi:10.1016/j.ijrobp.2020.04.013pmid:http://www.ncbi.nlm.nih.gov/pubmed/32311417
CrossRef PubMed Google Scholar
↵
1. Milosevic MF,
2. Townsley CA,
3. Chaudary N, et al
. Sorafenib increases tumor hypoxia in cervical cancer patients treated with radiation therapy: results of a phase 1 clinical study. Int J Radiat Oncol Biol Phys 2016;94:111–7.doi:10.1016/j.ijrobp.2015.09.009pmid:http://www.ncbi.nlm.nih.gov/pubmed/26547383
PubMed Google Scholar
↵
1. Gaffney DK,
2. Winter K,
3. Dicker AP, et al
. A phase II study of acute toxicity for Celebrex (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: primary endpoint analysis of RTOG 0128. Int J Radiat Oncol Biol Phys 2007;67:104–9.doi:10.1016/j.ijrobp.2006.08.002pmid:http://www.ncbi.nlm.nih.gov/pubmed/17084549
PubMed Google Scholar
↵
1. Begley CG,
2. Ashton M,
3. Baell J, et al
. Drug repurposing: misconceptions, challenges, and opportunities for academic researchers. Sci Transl Med 2021;13:eabd5524.doi:10.1126/scitranslmed.abd5524pmid:http://www.ncbi.nlm.nih.gov/pubmed/34550729
PubMed Google Scholar
↵
1. Stransky N,
2. Ruth P,
3. Schwab M, et al
. Can any drug be repurposed for cancer treatment? A systematic assessment of the scientific literature. Cancers 2021;13:6236.doi:10.3390/cancers13246236pmid:http://www.ncbi.nlm.nih.gov/pubmed/34944859
PubMed Google Scholar
↵
1. Parmar MKB,
2. Carpenter J,
3. Sydes MR
. More multiarm randomised trials of superiority are needed. Lancet 2014;384:283–4.doi:10.1016/S0140-6736(14)61122-3pmid:http://www.ncbi.nlm.nih.gov/pubmed/25066148
CrossRef PubMed Google Scholar
1. Huilgol NG,
2. Chatterjee N,
3. Singh BB
. Assessment of chlorpromazine as radiation sensitizer and protector. Indian J Cancer 1996;33:195–200.pmid:http://www.ncbi.nlm.nih.gov/pubmed/9255000
PubMed Google Scholar
1. Pohlmann P,
2. DiLeone LP,
3. Cancella AI, et al
. Phase II trial of cisplatin plus decitabine, a new DNA hypomethylating agent, in patients with advanced squamous cell carcinoma of the cervix. Am J Clin Oncol 2002;25:496–501.doi:10.1097/00000421-200210000-00015pmid:http://www.ncbi.nlm.nih.gov/pubmed/12393992
CrossRef PubMed Web of Science Google Scholar
1. Sharma DN,
2. Rath GK,
3. Julka PK, et al
. Role of gefitinib in patients with recurrent or metastatic cervical carcinoma ineligible or refractory to systemic chemotherapy: first study from Asia. Int J Gynecol Cancer 2013;23:705–9.doi:10.1097/IGC.0b013e31828b1699pmid:http://www.ncbi.nlm.nih.gov/pubmed/23466569
Abstract/FREE Full Text Google Scholar
1. Benson R,
2. Pathy S,
3. Kumar L, et al
. Locally advanced cervical cancer - neoadjuvant chemotherapy followed by concurrent chemoradiation and targeted therapy as maintenance: A phase II study. J Cancer Res Ther 2019;15:1359–64.doi:10.4103/jcrt.JCRT_39_18pmid:http://www.ncbi.nlm.nih.gov/pubmed/31898673
PubMed Google Scholar
1. Knox JJ,
2. Siu LL,
3. Chen E, et al
. A phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix. Eur J Cancer 2005;41:523–30.doi:10.1016/j.ejca.2004.12.013pmid:http://www.ncbi.nlm.nih.gov/pubmed/15737556
CrossRef PubMed Google Scholar
1. van Weelden WJ,
2. Sekarutami SM,
3. Bekkers RLM, et al
. The effect of carbogen breathing and nicotinamide added to standard (chemo)radiation treatment of advanced cervical cancer in Indonesia. Int J Gynecol Cancer 2014;24:1628–35.doi:10.1097/IGC.0000000000000271pmid:http://www.ncbi.nlm.nih.gov/pubmed/25244605
Abstract/FREE Full Text Google Scholar
1. Schaffer P,
2. Batash R,
3. Ertl-Wagner B, et al
. Treatment of cervix carcinoma FIGO IIIB with Photofrin II as a radiosensitizer: a case report. Photochem Photobiol Sci 2019;18:1275–9.doi:10.1039/C8PP00576Apmid:http://www.ncbi.nlm.nih.gov/pubmed/30892313
PubMed Google Scholar

Supplementary materials

Supplementary Data

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Data supplement 1

Footnotes

Contributors RC and GB drafted the manuscript. SP, IB, PP, SC, RN reviewed the manuscript and provided input on the manuscript. PP ran the queries and prepared the databases for off-line processing. RC and GB screened the abstracts and trials for relevance. RC and GB are the guarantors of the manuscript. All authors contributed to the manuscript and approved the submitted version.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests RN receives research grants from Dutch Research Council, Dutch Cancer Society, Varian, Elekta, Accuray and is an advisory board MSD: Global Gynecologic Cancer MDT Forum 2021.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.