Stem Cell Therapy in Breast Cancer

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StemCell Therapy in Breast Cancer

Abstract

Researchon stem cell therapy for breast cancer began in 2003 following thediscovery of self-regulating stem cells that influence the occurrenceand development of the breast cancer. The stem cell therapy isdefined as the use of stem cells to treat medical conditions (such ascancer), which is mainly achieved through the transplantation ofthese stem cells. Genetically modified hematopoietic stem cells (HSC)are able to reach the cancerous region and reduce the recruitment ofinflammatory cells into the tumor, thus controlling the growth of thetumor. Neural stem cells (NSC) could be used to transport5-fluorouracil, which is an anticancer agent, to the target site andsuccessfully reduce the mass of the breast cancer tumors. Mesenchymalstem cells (MSCs) can be used to deliver therapeutic agents to thecancerous sites, thus overcoming the issue of drug resistance amongpatients suffering from late-stage breast cancer. In vitrointroduction of MSCs in large quantities within the neoplastic sitesfueled the development of cancer, which raises doubt on theeffectiveness of stem cell therapy in treatment of breast cancer.MSCs could be used to transport sodium iodine to breast cancer tumorsin order to overcome resistance to chemotherapy by delivering thetherapeutic agent directly to the tumor. The relationship between theeffective recovery from breast cancer and the administration ofhigh-dose therapy with the support of stem cells was notstatistically significant. The use of hematopoietic stem cells tofacilitate the administration of high-dose chemotherapy in theprocess of treating advanced breast cancer had better than expectedresults, where 23 % of the subjects survived death while 18 % of themrecovered completely.

Keywords: Stem cell therapy, high-dose therapy, implantation, breastcancer.

StemCell Therapy in Breast Cancer

Thetreatment of the breast cancer has been a main challenge given thatsome patients develop resistance to chemotherapy, which makes thedelivery of the therapeutic agents or drugs to the targeted sites.This challenge has attracted many researchers who have been trying toidentify the possible methods of treating breast cancer, which is themost common types of tumor in the modern world (Li et al., 2009). Inspite of the numerous efforts and resources applied in the study ofthe breast cancer and its treatment, only a few of the proposedtreatment procedures have reached the clinical trials. The stem celltherapy is among the key areas of interest to the majority ofresearchers and scholars. Stem cells therapy refers to the use ofstem cells that are derived from other body parts (such as bonemarrow) to treat medical conditions, such as cancer. These stem cellsmay be infused with therapeutic agents or be genetically modifiedbefore being transplanted. Infusion and genetic modification give thestem cells the desired therapeutic properties and it is done in vitroin laboratory. The efforts to determine the effectiveness of stemcells in the treatment of the breast cancer began close to one and ahalf decades ago following the observation that the tumor stromaprevented drugs or therapeutic agents that were administeredintratumorally or systematically from reaching their targeted sites(Li et al., 2009). This paper will review seven journal articlesdocumenting research on stem cell trials in the treatment of breastcancer.

Goals

  • To assess the effectiveness of genetically modified hematopoietic stem cells in controlling the recruitment of inflammatory cells into tumors forming the breast cancer.

  • To assess the effectiveness of mesenchymal stem cells used as vehicles for transferring different therapeutic agents in the treatment of breast cancer.

  • To determine the effectiveness of using neural stem cells to deliver therapeutic genes in the treatment of breast cancer.

  • To determine the effectiveness of high-dose chemotherapy that is administered with the help of stem cells in the treatment of breast cancer at the advanced stage.

Methods

Thearticles used in this paper were obtained through an online search,where the key words and phrases, such as “the use stem cells intreatment of breast cancer” and “the stem cell therapy for breastcancer”. Authors of the seven articles described different methodsthrough which stem cell therapy is administered to patients sufferingfrom breast cancer. A preclinical trial conducted by Li (et al.,2009) focused on the transplantation of genetically modifiedhematopoietic stem cells (HSCs) into patients with the late-stagecancer. HSCs were genetically modified by inducing intratumoralexpression of relaxin. The introduction of these genetically modifiedstem cells was expected to control the recruitment of inflammatorycells in to the tumor.

Joo,Shin, Kim, Jin, Lee, Kim, Jo &amp Nam (2009) conducted a preclinicaltrial that involved the use of neural stem cells (NSC) as agents fordelivering therapeutic agents to target sites. This was accomplishedby making human NSC that could express cytosine deaminase that isresponsible for conversion of 5-fluorocytosine into 5-fluorouracil,which is an anticancer agent.

Madjd(et al., 2013) conducted a systematic review of articles thatdocumented clinical trials of the use of stem cell therapy for thetreatment of breast cancer. In these clinical trials, the stem cellswere transplanted with the objective of using them as carriers of thepharmaceutical products to areas of the body (breast region) thatsuffered from cancer. Mesenchymal stem cells (MSCs) were used asvehicles to transport different therapeutic products to regions thatare targeted through the proteasome-dependent suicide gene.

Kamdje,Etet &amp Lukong (2014) conducted a similar review of the use ofMSCs as agents for delivering therapeutic products to affected cells.However, the review included in vitro study that focused on theidentification of mechanisms through which MSCs support cancer cellsthat are actively dividing.

Dwyer,Ryan, Morris, Havelin, Miller, Flavin, Liu, Foley, Murphy, J.,O’Brien, T., Barry, P., &amp Kerin, J. (2011) conducted a trial onthe use of mesenchymal stem cells (MSCs) in transportation of sodiumiodine symporter to test the efficiency of stem cells in treatment ofbreast cancer. The NIS expressing mesenchymal stem cells wereimplanted through intratumoral injection, which was followed by99mTcO4- imaging 3-14Days.

Berry,Ueno, Lei, X., Johnson, Smith, Grump, Yancey, Biron, Schmid, Crown,Lotz, Rosti &amp Demirer (2011) reviewed six a randomized trial withthe objective of evaluating the effect of high dose chemotherapy withsupport from the transplant of stem cells in the treatment of breastcancer. In al randomized trials, the high chemotherapy wasfacilitated by the use of stem cells to transport pharmaceuticalproducts used in the treatment of breast cancer in the conventionaltreatment procedures. Therefore, the stem cells were only used tofacilitate the movement of drugs to the target tumor or sites.

Aclinical trial performed by Muller, Kohrt, Klein, J., Lapport, Cha,Guardino, Stockerl-Goldstein, Jutter, Hanania, Blume, Jutter,Negrin, Weissman &amp Shizuru (2012) aimed at assessing theeffectiveness of high-dose chemotherapy that was facilitated by thetransplantation of hematopoietic stem cells in the treatment ofbreast cancer. The stem cells (HSCs) were purified and infused withdrugs used in the treatment of breast cancer before being implanted.

Findings

Thepreclinical trial conducted by Li (et al., 2009) which wasaccomplished by introducing genetically modified HSCs indicated thatthe stem cells had the capacity to access the sites (breast regions)suffering from the tumor. Once on the site, the stem cells reducedthe recruitment of inflammatory cells into the tumor, thus reducingthe further growth of the tumor.

Theimplantation of the NSC cells in a preclinical trial conducted by Joo(etal.,2009) resulted in a significant decline in the size of the tumor. Theeffectiveness of the trial in containing the growth of the cancerouscells was associated by the use of stem cells to transport theanti-cancer agent known as 5-fluorouracil to the affected sites. TheNSC cells were able to migrate selectively to the brain metastasisthat is located in the opposite hemisphere and reduce the mass of thebreast tumor.

Thesystematic review of the research on clinical trials of the use ofstem cell therapy conducted by Madjd (et al., 2013) indicated thatthe MSCs cells carrying the therapeutic agents could be noticed inboth the targeted as well as non-targeted regions, such as the heartand the lungs. However, the stem cells that went to non-targetedregions were degraded within the first few days, which the stem cellsthat went the cancerous sites remained intact and effective, leadingto a noticeable decline in tumor size. This confirmed that stem cellscan be effectively used to deliver therapeutic agents to patients whoare suffering from resistant breast cancer.

Asimilar review of the use of MSCs cells to deliver therapeuticproducts to the regions of the body affected by the tumor confirmedthat these stem cells are reliable carries that can be used todeliver the drugs and help patients who have expressed resistance tochemotherapy (Kamdje, Etet &amp Lukong, 2014). However, a concernwas raised since it could be possible that the cells that result inbreast cancer result from MSCs, which implies that the use of thiscategory of stem cells could fuel the tumorigenic process, thusrendering the stem cell therapy for breast cancer counterproductive.The in vitro trials indicated that MSCs fueled tumorigenesis whenintroduced in large quantities to neoplastic sites.

Thegene expression of hNIS in a trial conducted by Dwyer (etal.,2011) was detected in the heart, the intestines, the lungs, and thetargeted tumors. However, the expression detected in the non-targetregions was depleted while the expression in the tumors persisted. Asignificant reduction in the size of the tumor was observed. Theresearchers recommended the MSCs mediated treated as a novel breastcancer therapy because the implanted stem cells carrying the sodiumiodine could be traced in real time.

Thereview of randomized trials conducted by Berry (etal.,2011) indicated that the high-dose chemotherapy that was administeredwith the help of stem cells was not statically significant. Thisimplies that the stem cell therapy had not survival therapy for theaffected subjects. The researchers concluded that the evidenceindicating that patients could benefit from the administration ofhigh-dose chemotherapy with the help of hematopoietic support was toolittle.

Theclinical trial of the high-dose chemotherapy that was conducted byMuller (etal.,2012) indicated that 23 % of the 22 women were alive after 12 yearsof receiving the HDCT, where 18 % of them are free from therecurrence of breast cancer. In addition, patients who wereidentified to be free from the risk of recurrence of the breastcancer had normal hematopoietic function. The researchers concludedthat the results were better than expected given that the patientsundergoing the trial suffered from breast cancer that had reachedadvanced stages following the failure of conventional treatmentsprocedures.

Discussion

Themain purpose of the present study was to explore the use of stemcells therapy in the treatment of breast cancer. All the studiesreviewed in the present study indicate that stem cell therapy iseffective in the treatment if the breast cancer compared to othertypes of therapy. It is evident that scientists can use two methodsto facilitate the treatment of breast cancer using the stem cells.The first and the most common method is infusion of stem cells withselected types of drugs and then implanting the stem cells into thepatient’s body. The only therapeutic advantage that is obtainedfrom the drug infusion method is the delivery of drugs directly tothe tumors. In this case stem cells serve as carriers while theregulation of the growth of the tumor is done by the drug like in theconventional chemotherapy. This method is desirable for patients whohave developed resistance to chemotherapy, and its effectiveness wasproven in trials reported by Joo (etal.,2009), Madjd (et al., 2013), Kamdje, Etet, &amp Lukong, 2014), Dwyer(et al., 2011), Berry (etal.,2011) and Muller (etal.,2012). The second method of genetic modification of stem cells is acompletely different therapeutic approach that seeks to control therecruitment of inflammatory cells into the tumor or introduce the setof cells that will divide normally. The success of geneticmodification in treating breast cancer has been shown by a trial doneby Li (et al., 2009).

Conclusion

Theuse of stem cell therapy in the treatment of breast cancer is stillunder-researched, and only a few of the studies have been triedclinically. Nevertheless, the laboratory studies that have beencompleted suggest that stem cells could be used to facilitate thedelivery therapeutic products to the sites with cancerous cells, thusovercoming the challenge of resistance to chemotherapy. In addition,further studies suggest that genetic modification might help in theregulation of expression of genes that result in the uncontrolledmultiplication of cancerous cells. Although most to the currentstudies are at the preclinical stage, it is evident that stem celltherapy will provide a viable solution to challenges (such as drugresistance and severe side effects) that the health care providersare facing when treating breast cancer. The most helpful stem cellsinclude neural stem cells (NSC), hematopoietic stem cells (HSC), andmesenchymal stem cells (MSCs). However, some fears have been raisedconcerning the use of mesenchymal stem cells since it is suspectedthat this stem cell contribute towards the occurrence of breastcancer. Therefore, stem cells could be viable in the treatment of thebreast cancer, but care should be taken to ensure that the treatmentis not counterproductive, especially when MSCs are used.

References

Berry,A., Ueno, T., Lei, X., Johnson, M., Smith, A., Grump, M., Yancey, J.,Biron, P., Schmid, P., Crown, P., Lotz, J., Rosti, G., &amp Demirer,T. (2011). High-dose chemotherapy with autologous hematopoietic stemcells transplantation in metastatic breast cancer: Overview of sixrandomized trials. Journalof Clinical Oncology,29, 1-9.

Dwyer,M., Ryan, J., Morris, C., Havelin, J., Miller, W., Flavin, R., Liu,Z., Foley, J., Murphy, J., O’Brien, T., Barry, P., &amp Kerin, J.(2011). Mesenchymal stem cell (MSC) mediated delivery of the sodiumiodine symporter (NIS) supports radionuclide imaging and treatment ofbreast cancer. StemCells,29 (7), 149-1157.

Joo,K., Shin, I., Kim, M., Jin, J., Lee, S., Kim, S., Jo, M. &amp Nam,D. (2009). Human neural stem cells can target and deliver therapeuticgenes to breast cancer brain. MolecularTherapy,17 (3), 570-575.

Kamdje,A., Etet, P., &amp Lukong, K. (2014). Mesenchymal stem cell therapyfor breast cancer: Challenges remaining. InternationalJournal of Biomedical Science and Engineering,2 (6), 20-24.

Li,Z., Tuve, S., Xun, Y., Feng, Q., Min, L., Kiviat, N., Disis, M.,kiem, H., &amp Lieber, A. (2009). Toward a stem cell gene therapyfor breast cancer. Blood,113 (22), 5422-5433.

Madjd,Z., Gheytanchi, E., Erfani, E., &amp Asadi-Lari, M. (2013).Application of stem cells in targeted therapy of breast cancer: Asystematic review. AsianPacific Journal of Cancer Prevention,14 (5), 2789-2800.

Muller,M., Kohrt, E., Klein, J., Lapport, G., Cha, S., Guardino, E.,Stockerl-Goldstein, E., Jutter, C., Hanania, E., Blume, G., Jutter,C., Negrin, S., Weissman, L. &amp Shizuru, A. (2012). Long-termoutcome of patients with metastatic breast cancer treatment withhigh-dose chemotherapy and transplantation of purified autologoushematopoietic stem cells. BiolBlood Marrow Transplant,18, 125-133.