Editing Chemotherapy (section)

== Research ==
[[File:Mesoporous silica SEM.jpg|thumb|[[Scanning electron micrograph]] of [[mesoporous silica]], a type of [[nanoparticle]] used in the delivery of chemotherapeutic drugs]]
{{Main|Experimental cancer treatments}}

=== Targeted delivery vehicles ===
Specially targeted delivery vehicles aim to increase effective levels of chemotherapy for tumor cells while reducing effective levels for other cells. This should result in an increased tumor kill or reduced toxicity or both.<ref name="pmid21501554">{{cite journal | vauthors = Chidambaram M, Manavalan R, Kathiresan K | title = Nanotherapeutics to overcome conventional cancer chemotherapy limitations | journal = Journal of Pharmacy & Pharmaceutical Sciences | volume = 14 | issue = 1 | pages = 67–77 | year = 2011 | pmid = 21501554 | doi = 10.18433/J30C7D | doi-access = free }}</ref>

==== Antibody-drug conjugates ====
[[Antibody-drug conjugate]]s (ADCs) comprise an [[antibody]], drug and a linker between them. The antibody will be targeted at a preferentially expressed protein in the tumour cells (known as a [[tumor antigen]]) or on cells that the tumor can utilise, such as blood vessel [[endothelial cells]]. They bind to the tumor antigen and are internalised, where the linker releases the drug into the cell. These specially targeted delivery vehicles vary in their stability, selectivity, and choice of target, but, in essence, they all aim to increase the maximum effective dose that can be delivered to the tumor cells.<ref name="pmid22003066">{{cite journal | vauthors = Teicher BA, Chari RV | title = Antibody conjugate therapeutics: challenges and potential | journal = Clinical Cancer Research | volume = 17 | issue = 20 | pages = 6389–97 | date = October 2011 | pmid = 22003066 | doi = 10.1158/1078-0432.CCR-11-1417 | doi-access = free }}</ref> Reduced systemic toxicity means that they can also be used in people who are sicker and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches.<ref>{{Cite journal |last1=Mokhtari |first1=Reza Bayat |last2=Homayouni |first2=Tina S. |last3=Baluch |first3=Narges |last4=Morgatskaya |first4=Evgeniya |last5=Kumar |first5=Sushil |last6=Das |first6=Bikul |last7=Yeger |first7=Herman |date=2017-03-30 |title=Combination therapy in combating cancer |journal=Oncotarget |volume=8 |issue=23 |pages=38022–38043 |doi=10.18632/oncotarget.16723 |issn=1949-2553 |pmc=5514969 |pmid=28410237}}</ref>

The first approved drug of this type was [[gemtuzumab ozogamicin]] (Mylotarg), released by [[Wyeth]] (now [[Pfizer]]). The drug was approved to treat [[acute myeloid leukemia]].<ref name="pmid11673694">{{cite journal | vauthors = Sievers EL, Linenberger M | title = Mylotarg: antibody-targeted chemotherapy comes of age | journal = Current Opinion in Oncology | volume = 13 | issue = 6 | pages = 522–7 | date = November 2001 | pmid = 11673694 | doi = 10.1097/00001622-200111000-00016 | s2cid = 27827980 }}</ref> Two other drugs, [[trastuzumab emtansine]] and [[brentuximab vedotin]], are both in late clinical trials, and the latter has been granted accelerated approval for the treatment of [[refractory]] [[Hodgkin's lymphoma]] and systemic [[anaplastic large cell lymphoma]].<ref name="pmid22003066" />

==== Nanoparticles ====
[[Nanoparticles]] are 1–1000 [[nanometer]] (nm) sized particles that can promote tumor selectivity and aid in delivering low-[[solubility]] drugs. Nanoparticles can be targeted passively or actively. Passive targeting exploits the difference between tumor blood vessels and normal blood vessels. Blood vessels in tumors are "leaky" because they have gaps from 200 to 2000&nbsp;nm, which allow nanoparticles to escape into the tumor. Active targeting uses biological molecules ([[Antibody|antibodies]], [[protein]]s, [[DNA]] and [[receptor ligand]]s) to preferentially target the nanoparticles to the tumor cells. There are many types of nanoparticle delivery systems, such as [[mesoporous silica|silica]], [[polymer]]s, [[liposome]]s<ref name="pmid35457065">{{cite journal | vauthors = Taléns-Visconti R, Díez-Sales O, de Julián-Ortiz JV, Nácher A | title = Nanoliposomes in Cancer Therapy: Marketed Products and Current Clinical Trials | journal = International Journal of Molecular Sciences | volume = 23 | issue = 8 | pages = 4249 | date = Apr 2022 | doi = 10.3390/ijms23084249 | pmid = 35457065 | pmc = 9030431 | doi-access = free }}</ref> and magnetic particles. Nanoparticles made of magnetic material can also be used to concentrate agents at tumor sites using an externally applied magnetic field.<ref name="pmid21501554" /> They have emerged as a useful vehicle in [[magnetic drug delivery]] for poorly soluble agents such as [[paclitaxel]].<ref name="pmid19554862">{{cite journal | vauthors = Vines T, Faunce T | title = Assessing the safety and cost-effectiveness of early nanodrugs | journal = Journal of Law and Medicine | volume = 16 | issue = 5 | pages = 822–45 | date = May 2009 | pmid = 19554862 }}</ref>

=== Electrochemotherapy ===
{{Main|Electrochemotherapy}}
Electrochemotherapy is the combined treatment in which injection of a chemotherapeutic drug is followed by application of high-voltage electric pulses locally to the tumor. The treatment enables the chemotherapeutic drugs, which otherwise cannot or hardly go through the membrane of cells (such as bleomycin and cisplatin), to enter the cancer cells. Hence, greater effectiveness of antitumor treatment is achieved.<ref name="Whelan"/>

Clinical electrochemotherapy has been successfully used for treatment of cutaneous and subcutaneous tumors irrespective of their histological origin.<ref name="Whelan">{{cite journal | vauthors = Larkin JO, Collins CG, Aarons S, Tangney M, Whelan M, O'Reily S, Breathnach O, Soden DM, O'Sullivan GC | title = Electrochemotherapy: aspects of preclinical development and early clinical experience | journal = Annals of Surgery | volume = 245 | issue = 3 | pages = 469–79 | date = March 2007 | pmid = 17435555 | pmc = 1877027 | doi = 10.1097/01.sla.0000250419.36053.33 }}</ref><ref>{{cite journal | vauthors = Testori A, Tosti G, Martinoli C, Spadola G, Cataldo F, Verrecchia F, Baldini F, Mosconi M, Soteldo J, Tedeschi I, Passoni C, Pari C, Di Pietro A, Ferrucci PF | title = Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach | journal = Dermatologic Therapy | volume = 23 | issue = 6 | pages = 651–61 | year = 2010 | pmid = 21054709 | doi = 10.1111/j.1529-8019.2010.01370.x | s2cid = 46534637 | doi-access = free }}</ref> The method has been reported as safe, simple and highly effective in all reports on clinical use of electrochemotherapy. According to the ESOPE project (European Standard Operating Procedures of Electrochemotherapy), the Standard Operating Procedures (SOP) for electrochemotherapy were prepared, based on the experience of the leading European cancer centres on electrochemotherapy.<ref name="Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, Billard V, Geertsen PF, Larkin JO, Miklavcic D, Pavlovic I, Paulin-Kosir SM, Cemazar M, Morsli N, Soden DM, Rudolf Z, Robert C, O'Sullivan GC, Mir LM. 2006">{{cite journal |vauthors=Marty M, Sersa G, Garbay JR, Gehl J, Collins CG, Snoj M, Billard V, Geertsen PF, Larkin JO, Miklavcic D, Pavlovic I, Paulin-Kosir SM, Cemazar M, Morsli N, Soden DM, Rudolf Z, Robert C, O'Sullivan GC, Mir LM |year=2006 |title=Electrochemotherapy – An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases |journal=Eur J Cancer Suppl |volume=4 |issue=11 |pages=3–13 |doi=10.1016/j.ejcsup.2006.08.002}}</ref><ref>{{cite journal |vauthors=Mir LM, Gehl J, Sersa G, Collins CG, Garbay JR, Billard V, Geertsen PF, Rudolf Z, O'Sullivan GC, Marty M |title=Standard operating procedures of the electrochemotherapy: Instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the Cliniporator™ by means of invasive or non-invasive electrodes |journal=Eur J Cancer Suppl |volume=4 |issue=11 |pages=14–25 |year=2006 |doi=10.1016/j.ejcsup.2006.08.003 }}</ref> Recently, new electrochemotherapy modalities have been developed for treatment of internal tumors using surgical procedures, endoscopic routes or percutaneous approaches to gain access to the treatment area.<ref>{{cite journal | vauthors = Soden DM, Larkin JO, Collins CG, Tangney M, Aarons S, Piggott J, Morrissey A, Dunne C, O'Sullivan GC | title = Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours | journal = Cancer Letters | volume = 232 | issue = 2 | pages = 300–10 | date = February 2006 | pmid = 15964138 | doi = 10.1016/j.canlet.2005.03.057 }}</ref><ref>{{cite journal | vauthors = Miklavcic D, Snoj M, Zupanic A, Kos B, Cemazar M, Kropivnik M, Bracko M, Pecnik T, Gadzijev E, Sersa G | title = Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy | journal = BioMedical Engineering OnLine | volume = 9 | issue = 1 | pages = 10 | date = February 2010 | pmid = 20178589 | pmc = 2843684 | doi = 10.1186/1475-925X-9-10 | doi-access = free }}</ref>

=== Hyperthermia therapy ===
[[Hyperthermia therapy]] is heat treatment for cancer that can be a powerful tool when used in combination with chemotherapy (thermochemotherapy) or radiation for the control of a variety of cancers. The heat can be applied locally to the tumor site, which will dilate blood vessels to the tumor, allowing more chemotherapeutic medication to enter the tumor. Additionally, the tumor cell membrane will become more porous, further allowing more of the chemotherapeutic medicine to enter the tumor cell.

Hyperthermia has also been shown to help prevent or reverse "chemo-resistance." Chemotherapy resistance sometimes develops over time as the tumors adapt and can overcome the toxicity of the chemo medication. "Overcoming chemoresistance has been extensively studied within the past, especially using CDDP-resistant cells. In regard to the potential benefit that drug-resistant cells can be recruited for effective therapy by combining chemotherapy with hyperthermia, it was important to show that chemoresistance against several anticancer drugs (e.g. mitomycin C, anthracyclines, BCNU, melphalan) including CDDP could be reversed at least partially by the addition of heat.<ref>{{cite journal| vauthors = Issels R |title=Hyperthermia Combined with Chemotherapy – Biological Rationale, Clinical Application, and Treatment Results |journal=Onkologie |year=1999 |volume=22 |issue=5 |pages=374–381 |doi=10.1159/000026986 |s2cid=37581171 |url=http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-16495-8 }}</ref>