Abstract
Colorectal Cancer (CRC) has a high mortality rate and is one of the most difficult diseases to manage due to tumour resistance and metastasis. The treatment of choice for CRC is reliant on the phase and time of diagnosis. Despite several conventional treatments available to treat CRC (surgical excision, chemo-, radiationand immune-therapy), resistance is a major challenge, especially if it has metastasized. Additionally, these treatments often cause unwanted adverse side effects and so it remains imperative to investigate alternative combination therapies.
Photodynamic Therapy (PDT) is a promising treatment modality for the primary treatment of CRC, since it is non-invasive, has few side effects and selectively damages only cancerous tissues, leaving adjacent healthy structures intact. PDT involves three fundamentals: a Photosensitizer (PS) drug localized in tumour tissues, oxygen, and light. Upon PS excitation using a specific wavelength of light, an energy transfer cascade occurs, that ultimately yields cytotoxic species, which in turn induces cell death. Cannabidiol (CBD) is a cannabinoid compound derived from the Cannabis sativa plant, which has shown to exert anticancer effects on CRC through different pathways, inducing apoptosis and so inhibiting tumour metastasis and secondary spread.
This review paper highlights current conventional treatment modalities for CRC and their limitations, as well as discusses the necessitation for further investigation into unconventional active nanoparticle targeting PDT treatments for enhanced primary CRC treatment. This can be administered in combination with CBD, to prevent CRC secondary spread and enhance the synergistic efficacy of CRC treatment outcomes, with less side effects.
Keywords: Colorectal Cancer (CRC), combinative treatment, Cannabis sativa, Cannabidiol (CBD), Photodynamic Therapy (PDT), targeted therapy.
Graphical Abstract
[http://dx.doi.org/10.1038/s41392-017-0004-3] [PMID: 29560283]
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[PMID: 27766137]
[http://dx.doi.org/10.1016/j.critrevonc.2012.09.014] [PMID: 23098684]
[http://dx.doi.org/10.1177/1010428317734691]] [PMID: 28990490]
[http://dx.doi.org/10.3390/ijms18010197] [PMID: 28106826]
[http://dx.doi.org/10.1038/nrdp.2015.65] [PMID: 27189416]
[http://dx.doi.org/10.2147/CIA.S109285] [PMID: 27486317]
[http://dx.doi.org/10.1016/j.ctrv.2019.02.002] [PMID: 30849607]
[PMID: 10.3892/or.2015.4108] [PMID: 26151224]
[http://dx.doi.org/10.1093/annonc/mdx052] [PMID: 28453697]
[http://dx.doi.org/10.1016/j.biopha.2018.08.006] [PMID: 30099345]
[http://dx.doi.org/10.1016/j.ejmech.2017.12.039] [PMID: 29289883]
[http://dx.doi.org/10.1159/000446490] [PMID: 27493946]
[PMID: 27330292]
[http://dx.doi.org/10.1055/s-0033-1348050]
[http://dx.doi.org/10.3889/oamjms.2017.122] [PMID: 28785349]
[http://dx.doi.org/10.7150/ijms.3635] [PMID: 22408567]
[http://dx.doi.org/10.3857/roj.2017.00395] [PMID: 29325395]
[http://dx.doi.org/10.6004/jnccn.2009.0058] [PMID: 19755048]
[http://dx.doi.org/10.1080/02841860701348670] [PMID: 17497318]
[http://dx.doi.org/10.1016/j.ijrobp.2009.03.010] [PMID: 19540058]
[http://dx.doi.org/10.3390/ijms18030656] [PMID: 28304343]
[http://dx.doi.org/10.1177/1533033818791795]] [PMID: 30099929]
[http://dx.doi.org/10.1089/cbr.2017.2210] [PMID: 28622036]
[http://dx.doi.org/10.4251/wjgo.v8.i9.642] [PMID: 27672422]
[http://dx.doi.org/10.2174/1381612819999131218175905] [PMID: 23755727]
[http://dx.doi.org/10.1155/2016/7590245]] [PMID: 27127793]
[http://dx.doi.org/10.1186/1878-5085-4-3] [PMID: 23356214]
[http://dx.doi.org/10.1371/journal.pone.0137053]] [PMID: 26381396]
[http://dx.doi.org/10.1159/000354995] [PMID: 26674429]
[http://dx.doi.org/10.1245/s10434-019-07209-x] [PMID: 30719633]
[http://dx.doi.org/10.1016/j.biopha.2018.07.049] [PMID: 30119176]
[http://dx.doi.org/10.1016/j.pdpdt.2019.04.033] [PMID: 31063860]
[http://dx.doi.org/10.1016/j.apsb.2016.01.007] [PMID: 27471670]
[http://dx.doi.org/10.1155/2014/383027]
[http://dx.doi.org/10.3390/molecules23102628] [PMID: 30322132]
[http://dx.doi.org/10.1016/B978-0-323-42864-4.00001-4]
[http://dx.doi.org/10.1042/BJ20150942] [PMID: 26862179]
[http://dx.doi.org/10.1111/j.1751-1097.2009.00585.x] [PMID: 19682322]
[PMID: 21498693]
[http://dx.doi.org/10.1007/s10103-018-2524-7] [PMID: 29796953]
[http://dx.doi.org/10.1016/j.pdpdt.2018.10.012]
[PMID: 25663983]
[http://dx.doi.org/10.1016/j.pdpdt.2018.07.007] [PMID: 30016752]
[http://dx.doi.org/10.1186/s12885-015-1514-4] [PMID: 26149077]
[http://dx.doi.org/10.1016/j.pdpdt.2018.01.010] [PMID: 29355734]
[http://dx.doi.org/10.7150/ijbs.27156] [PMID: 30662343]
[http://dx.doi.org/10.1016/j.pdpdt.2011.04.003] [PMID: 22122915]
[http://dx.doi.org/10.1016/j.pdpdt.2018.06.008] [PMID: 29894822]
[http://dx.doi.org/10.1016/j.jds.2013.10.005]
[http://dx.doi.org/10.3892/or.2013.2220] [PMID: 23291627]
[http://dx.doi.org/10.1159/000362416] [PMID: 24820409]
[http://dx.doi.org/10.1039/C6CS00271D] [PMID: 27722328]
[http://dx.doi.org/10.1186/s40824-018-0140-z] [PMID: 30275968]
[http://dx.doi.org/10.4161/auto.28679] [PMID: 24905352]
[http://dx.doi.org/10.1007/s00262-014-1633-9] [PMID: 25384911]
[http://dx.doi.org/10.1016/j.canlet.2019.01.011] [PMID: 30660647]
[http://dx.doi.org/10.1155/2019/3702518]
[http://dx.doi.org/10.2174/1389200217666160619191853] [PMID: 27335116]
[http://dx.doi.org/10.1016/j.jsps.2017.10.012] [PMID: 29379334]
[http://dx.doi.org/10.1080/10717544.2018.1477857] [PMID: 29869539]
[http://dx.doi.org/10.2147/IJN.S165210] [PMID: 30013345]
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[http://dx.doi.org/10.1186/1477-3155-11-41] [PMID: 24341795]
[http://dx.doi.org/10.1039/C8PP00271A] [PMID: 30118115]
[http://dx.doi.org/10.1039/C2NJ40984D]
[http://dx.doi.org/10.1039/c1dt11151e] [PMID: 21971707]
[PMID: 21499420]
[http://dx.doi.org/10.1186/2228-5326-3-45]
[http://dx.doi.org/10.1007/978-3-319-22942-3_4]
[http://dx.doi.org/10.1016/j.biopha.2016.07.058] [PMID: 27522005]
[http://dx.doi.org/10.1016/j.pdpdt.2015.07.175] [PMID: 26238625]
[http://dx.doi.org/10.2217/nnm-2017-0043] [PMID: 28703636]
[PMID: 23780966]
[http://dx.doi.org/10.1007/s00432-014-1767-3] [PMID: 25005786]
[http://dx.doi.org/10.4155/bio.13.37] [PMID: 23641699]
[http://dx.doi.org/10.1155/2013/863951]
[http://dx.doi.org/10.1080/2162402X.2016.1227897]] [PMID: 27853651]
[http://dx.doi.org/10.1371/journal.pone.0189953]] [PMID: 29261789]
[http://dx.doi.org/10.1016/j.toxlet.2010.02.012] [PMID: 20184945]
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.06.023] [PMID: 29940353]
[http://dx.doi.org/10.4236/pp.2014.58091]
[http://dx.doi.org/10.1002/cam4.1312] [PMID: 29473338]
[http://dx.doi.org/10.1186/s12906-016-1280-0] [PMID: 27586579]
[http://dx.doi.org/10.21873/anticanres.12924] [PMID: 30275207]
[http://dx.doi.org/10.1111/j.1365-2125.2012.04298.x] [PMID: 22506672]
[http://dx.doi.org/10.1158/1535-7163.MCT-10-1100] [PMID: 21566064]
[http://dx.doi.org/10.1007/s00109-011-0856-x] [PMID: 22231745]
[http://dx.doi.org/10.1016/j.jocn.2019.02.019] [PMID: 30837109]
[http://dx.doi.org/10.1186/1756-8722-5-63] [PMID: 23057939]
[http://dx.doi.org/10.3390/biomedicines5020034] [PMID: 28635679]
[http://dx.doi.org/10.1111/j.1476-5381.2012.02050.x]] [PMID: 22624859]
[http://dx.doi.org/10.1016/j.phymed.2013.11.006] [PMID: 24373545]
[http://dx.doi.org/10.1007/s00580-018-2810-6]
[http://dx.doi.org/10.3748/wjg.v23.i10.1780] [PMID: 28348483]
[PMID: 30651763]
[http://dx.doi.org/10.1038/cdd.2015.174] [PMID: 26943322]
[http://dx.doi.org/10.3390/cancers11050642] [PMID: 31075907]
[http://dx.doi.org/10.3390/cancers11060781] [PMID: 31195721]
[http://dx.doi.org/10.1016/j.bbamcr.2018.05.007] [PMID: 29758299]
[http://dx.doi.org/10.18632/oncotarget.15393] [PMID: 28412728]
[http://dx.doi.org/10.1016/j.jconrel.2015.03.008] [PMID: 25758331]