Editing Experimental cancer treatment (section)

==Drug therapies==

===HAMLET (human alpha-lactalbumin made lethal to tumor cells)===
{{Main|HAMLET (human alpha-lactalbumin made lethal to tumor cells)}}
HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human [[breast milk]] that kills tumor cells by a process resembling programmed cell death ([[apoptosis]]). {{As of|2008}}, it had been tested in humans with skin [[papilloma]]s and [[bladder cancer]].<ref name=Hallgren>
{{cite book | vauthors = Hallgren O, Aits S, Brest P, Gustafsson L, Mossberg AK, Wullt B, Svanborg C | title = Bioactive Components of Milk | chapter = Apoptosis and Tumor Cell Death in Response to HAMLET (Human α-Lactalbumin Made Lethal to Tumor Cells) | volume = 606 | pages = 217–40 | year = 2008 | pmid = 18183931 | doi = 10.1007/978-0-387-74087-4_8 | isbn = 978-0-387-74086-7 | series = Advances in Experimental Medicine and Biology }}</ref>

===p53 activation therapy===
{{See also|Pramlintide}}
Several drug therapies are being developed based on [[p53]], the [[tumour suppressor gene]] that protects the cell in response to damage and stress. It is analogous to deciding what to do with a damaged car: p53 brings everything to a halt, and then decides whether to fix the cell or, if the cell is beyond repair, to destroy the cell. This protective function of p53 is disabled in most cancer cells, allowing them to multiply without check. Restoration of p53 activity in tumours (where possible) has been shown to inhibit tumour growth and can even shrink the tumour.<ref>{{cite journal | vauthors = Martins CP, Brown-Swigart L, Evan GI | title = Modeling the therapeutic efficacy of p53 restoration in tumors | journal = Cell | volume = 127 | issue = 7 | pages = 1323–34 | date = December 2006 | pmid = 17182091 | doi = 10.1016/j.cell.2006.12.007 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T | title = Restoration of p53 function leads to tumour regression in vivo | journal = Nature | volume = 445 | issue = 7128 | pages = 661–5 | date = February 2007 | pmid = 17251932 | doi = 10.1038/nature05541 | s2cid = 4373520 }}</ref><ref>{{cite journal | vauthors = Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW | title = Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas | journal = Nature | volume = 445 | issue = 7128 | pages = 656–60 | date = February 2007 | pmid = 17251933 | pmc = 4601097 | doi = 10.1038/nature05529 }}</ref>

As p53 protein levels are usually kept low, one could block its degradation and allow large amounts of p53 to accumulate, thus stimulating p53 activity and its antitumour effects. Drugs that utilize this mechanism include [[nutlin]] and MI-219, which are both in phase I [[clinical trials]].<ref>{{cite journal | vauthors = Brown CJ, Lain S, Verma CS, Fersht AR, Lane DP | title = Awakening guardian angels: drugging the p53 pathway | journal = Nature Reviews. Cancer | volume = 9 | issue = 12 | pages = 862–73 | date = December 2009 | pmid = 19935675 | doi = 10.1038/nrc2763 | s2cid = 205468654 }}</ref> {{As of|2009}}, there are also other drugs that are still in the preclinical stage of testing, such as RITA<ref>{{cite journal | vauthors = Issaeva N, Bozko P, Enge M, Protopopova M, Verhoef LG, Masucci M, Pramanik A, Selivanova G | title = Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors | journal = Nature Medicine | volume = 10 | issue = 12 | pages = 1321–8 | date = December 2004 | pmid = 15558054 | doi = 10.1038/nm1146 | s2cid = 82043 }}</ref> and MITA.<ref>{{cite journal | vauthors = Hedström E, Issaeva N, Enge M, Selivanova G | title = Tumor-specific induction of apoptosis by a p53-reactivating compound | journal = Experimental Cell Research | volume = 315 | issue = 3 | pages = 451–61 | date = February 2009 | pmid = 19071110 | doi = 10.1016/j.yexcr.2008.11.009 }}</ref>

===BI811283===
[[BI811283]] is a [[small molecule]] [[Enzyme inhibitor|inhibitor]] of the [[aurora B kinase]] protein being developed by [[Boehringer Ingelheim]] for use as an [[Anti-cancer drug|anti-cancer agent]]. {{As of|2010}}, BI 811283 is currently in the early stages of [[clinical development]] and is undergoing first-in-human trials in patients with [[solid tumor]]s and [[Acute myeloid leukemia|Acute Myeloid Leukaemia]].<ref name="one">{{Cite journal | volume = 28 | issue = 15 Suppl e13632 | pages = e13632 | vauthors = Gürtler U, Tontsch-Grunt U, Jarvis M, Zahn SK, Boehmelt G, Quant J, Adolf GR, Solca F | title = Effect of BI 811283, a novel inhibitor of Aurora B kinase, on tumor senescence and apoptosis | journal = J. Clin. Oncol. | year = 2010 | doi = 10.1200/jco.2010.28.15_suppl.e13632 }}
</ref>

=== Itraconazole ===
[[Itraconazole]], sometimes abbreviated ITZ, is an [[antifungal medication]] used to treat a number of [[fungal infections]]. Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the [[hedgehog pathway]] in a similar way to [[Sonidegib]].<ref>{{Cite journal|last1=Li|first1=Ke|last2=Fang|first2=Dengyang|last3=Xiong|first3=Zuming|last4=Luo|first4=Runlan|date=2019-08-23|title=Inhibition of the hedgehog pathway for the treatment of cancer using Itraconazole|journal=OncoTargets and Therapy|volume=12|pages=6875–6886|doi=10.2147/OTT.S223119|issn=1178-6930|pmc=6711563|pmid=31692536 |doi-access=free }}</ref>

===Selective androgen receptor modulators===
The majority of [[breast cancer]]s are [[androgen receptor]] (AR) positive and SARMs may help treat these cancers, although promising results have only been obtained with cancers that are both [[estrogen receptor]] (ER) positive and AR positive.<ref name=Solomon>{{cite journal |last1=Solomon |first1=Zachary J. |last2=Mirabal |first2=Jorge Rivera |last3=Mazur |first3=Daniel J. |last4=Kohn |first4=Taylor P. |last5=Lipshultz |first5=Larry I. |last6=Pastuszak |first6=Alexander W. |title=Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications |journal=Sexual Medicine Reviews |date=2019 |volume=7 |issue=1 |pages=84–94 |doi=10.1016/j.sxmr.2018.09.006|pmid=30503797 |pmc=6326857 }}</ref><ref name="Dai">{{cite journal |last1=Dai |first1=Charles |last2=Ellisen |first2=Leif W |title=Revisiting Androgen Receptor Signaling in Breast Cancer |journal=The Oncologist |date=2023 |volume=28 |issue=5 |pages=383–391 |doi=10.1093/oncolo/oyad049 |pmid=36972361 |pmc=10166165 |url=https://academic.oup.com/oncolo/article/28/5/383/7087214}}</ref> [[Anabolic androgenic steroids]] (AAS) were historically used successfully to treat AR positive breast cancer, but were phased out after the development of anti-estrogen therapies, due to androgenic side effects and concerns about [[aromatization]] to estrogen.  SARMs have some of the same therapeutic effects as AAS, but fewer side effects, and they cannot be aromatized.<ref name="Dai" /><ref name =trans>{{cite journal |last1=Christiansen |first1=Andrew R. |last2=Lipshultz |first2=Larry I. |last3=Hotaling |first3=James M. |last4=Pastuszak |first4=Alexander W. |title=Selective androgen receptor modulators: the future of androgen therapy? |journal=Translational Andrology and Urology |date=March 2020 |volume=9 |issue=Suppl 2 |pages=S135–S148 |doi=10.21037/tau.2019.11.02 |pmid=32257854 |pmc=7108998 |issn=2223-4683 |doi-access=free }}</ref><ref name=Narayanan>{{cite journal |last1=Narayanan |first1=Ramesh |last2=Coss |first2=Christopher C. |last3=Dalton |first3=James T. |title=Development of selective androgen receptor modulators (SARMs) |journal=Molecular and Cellular Endocrinology |date=2018 |volume=465 |pages=134–142 |doi=10.1016/j.mce.2017.06.013|pmid=28624515 |pmc=5896569 }}</ref> Although a trial on AR positive [[triple negative breast cancer]] was ended early due to lack of efficacy, ostarine showed benefits in some patients with ER+, AR+ [[metastatic]] breast cancer in a phase II study. In patients with more than 40 percent AR positivity as determined by [[immunohistochemistry]], the [[clinical benefit rate]] (CBR) was 80 percent and the [[objective response rate]] (ORR) was 48 percent—which was considered promising given that the patients had advanced disease and had been heavily pretreated.<ref>{{cite journal |last1=Palmieri |first1=Carlo |last2=Linden |first2=Hannah M. |last3=Birrell |first3=Stephen |last4=Lim |first4=Elgene |last5=Schwartzberg |first5=Lee S. |last6=Rugo |first6=Hope S. |last7=Cobb |first7=Patrick Wayne |last8=Jain |first8=Kirti |last9=Vogel |first9=Charles L. |last10=O'Shaughnessy |first10=Joyce |last11=Johnston |first11=Stephen R. D. |last12=Getzenberg |first12=Robert H. |last13=Barnette |first13=K. Gary |last14=Steiner |first14=Mitchell S. |last15=Brufsky |first15=Adam |last16=Overmoyer |first16=Beth |title=Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study. |journal=Journal of Clinical Oncology |date=2021 |volume=39 |issue=15_suppl |pages=1020 |doi=10.1200/JCO.2021.39.15_suppl.1020 |s2cid=236407030 |url=https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.1020 |language=en |issn=0732-183X}}</ref><ref name="Dai"/> In 2022, the FDA granted [[Fast track (FDA)|fast track designation]] to ostarine for AR+, [[Estrogen receptor|ER]]+, [[HER2]]- [[metastatic]] breast cancer.<ref>{{cite web |title=FDA Grants Fast Track Designation to Enobosarm in AR+, ER+, HER2- Metastatic Breast Cancer |url=https://www.cancernetwork.com/view/fda-grants-fast-track-designation-to-enobosarm-in-ar-er-her2--metastatic-breast-cancer |website=Cancer Network |access-date=27 August 2023 |language=en |date=10 January 2022}}</ref> SARMs have also shown antitumor effects in prostate cancer.<ref>{{cite journal |last1=Nyquist |first1=Michael D. |last2=Ang |first2=Lisa S. |last3=Corella |first3=Alexandra |last4=Coleman |first4=Ilsa M. |last5=Meers |first5=Michael P. |last6=Christiani |first6=Anthony J. |last7=Pierce |first7=Cordell |last8=Janssens |first8=Derek H. |last9=Meade |first9=Hannah E. |last10=Bose |first10=Arnab |last11=Brady |first11=Lauren |last12=Howard |first12=Timothy |last13=De Sarkar |first13=Navonil |last14=Frank |first14=Sander B. |last15=Dumpit |first15=Ruth F. |last16=Dalton |first16=James T. |last17=Corey |first17=Eva |last18=Plymate |first18=Stephen R. |last19=Haffner |first19=Michael C. |last20=Mostaghel |first20=Elahe A. |last21=Nelson |first21=Peter S. |title=Selective androgen receptor modulators activate the canonical prostate cancer androgen receptor program and repress cancer growth |journal=The Journal of Clinical Investigation |date=2021 |volume=131 |issue=10 |pages=e146777 |doi=10.1172/JCI146777 |pmid=33998604 |pmc=8121509 |issn=0021-9738}}</ref>