Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.
Cancer is a multi-stage process resulting from aberrant signaling pathways driving uncontrolled proliferation of transformed cells. The development and progression of cancer from a premalignant lesion towards a metastatic tumor requires accumulation of mutations in many regulatory genes of the cell. Different chemopreventative approaches have been sought to interfere with initiation and control malignant progression. Here we present research on dietary compounds with evidence of cancer prevention activity that highlights the potential beneficial effect of a diet rich in cruciferous vegetables. The Brassica family of cruciferous vegetables such as broccoli is a rich source of glucosinolates, which are metabolized to isothiocyanate compounds. Amongst a number of related variants of isothiocyanates, sulforaphane (SFN) has surfaced as a particularly potent chemopreventive agent based on its ability to target multiple mechanisms within the cell to control carcinogenesis. Anti-inflammatory, pro-apoptotic and modulation of histones are some of the more important and known mechanisms by which SFN exerts chemoprevention. The effect of SFN on cancer stem cells is another area of interest that has been explored in recent years and may contribute to its chemopreventive properties. In this paper, we briefly review structure, pharmacology and preclinical studies highlighting chemopreventive effects of SFN.
BackgroundNeuroblastoma (NB), a tumor of the primitive neural crest, despite aggressive treatment portends a poor long-term survival for patients with advanced high stage NB. New treatment strategies are required.MethodsWe investigated coordinated targeting of essential homeostatic regulatory factors involved in cancer progression, histone deacetylases (HDACs) and carbonic anhydrases (CAs).ResultsWe evaluated the antitumor potential of the HDAC inhibitor (HDACi), pyridylmethyl-N-{4-[(2-aminophenyl)-carbamoyl]-benzyl}-carbamate (MS-275) in combination with a pan CA inhibitor, acetazolamide (AZ) on NB SH-SY5Y, SK-N-SH and SK-N-BE(2) cells. The key observation was that the combination AZ + MS-275 significantly inhibited growth, induced cell cycle arrest and apoptosis, and reduced migration capacity of NB cell line SH-SY5Y. In addition, this combination significantly inhibited tumor growth in vivo, in a pre-clinical xenograft model. Evidence was obtained for a marked reduction in tumorigenicity and in the expression of mitotic, proliferative, HIF-1α and CAIX. NB xenografts of SH-SY5Y showed a significant increase in apoptosis.ConclusionMS-275 alone at nanomolar concentrations significantly reduced the putative cancer stem cell (CSC) fraction of NB cell lines, SH-SY5Y and SK-N-BE(2), in reference to NT2/D1, a teratocarcinoma cell line, exhibiting a strong stem cell like phenotype in vitro. Whereas stemness genes (OCT4, SOX2 and Nanog) were found to be significantly downregulated after MS-275 treatment, this was further enhanced by AZ co-treatment. The significant reduction in initial tumorigenicity and subsequent abrogation upon serial xenografting suggests potential elimination of the NB CSC fraction. The significant potentiation of MS-275 by AZ is a promising therapeutic approach and one amenable for administration to patients given their current clinical utility.
In the original publication the nickname of the 4th author was used instead of her real name-Zhenya Morgatskaya should be Evgeniya Morgatskaya.
ObjectiveTo explore experiences participating in a group-based physiotherapist (PT)-led exercise programme among people living with HIV and complex multimorbidity.DesignWe conducted a qualitative descriptive study using semistructured interviews.Recruitment and settingWe recruited community-dwelling adults living with HIV who engaged in a group-based PT-led exercise programme within an HIV-specialty hospital in Toronto, Canada. Interviews were conducted in-person or by telephone.ParticipantsEight men and two women with a median age of 58 years and median of six concurrent conditions in addition to HIV, who had attended ≥2 classes of the exercise programme.Data collectionInterviews explored (1) reasons for engaging in the programme, (2) experiences with exercise prior to and after joining the programme, (3) facilitators and barriers to engagement and (4) perceived impacts of participation on health and disability. We administered the HIV Disability Questionnaire and a demographic questionnaire.ResultsExperiences spanned perspectives prior to, during and after the PT-led exercise programme. Reasons for engaging in the programme included addressing health-related goals. Participants identified accessibility, the flexible schedule, interprofessional staff and the HIV-specific, group-based environment as facilitators to engagement. Participants reported high attendance rates, but identified episodic health challenges and overcrowded space as potential barriers to attending exercise classes. Perceived impacts on health and disability outcomes included improved physical, mental, social and cognitive health, and activities of daily living. Anticipated or actual experiences transitioning to independent exercise included facilitators (supportive programme leaders) and barriers (challenges motivatiing self to exercise alone).ConclusionsFeatures of the programme that facilitated engagement included the interprofessional, group-based environment that offered tailored exercise in an HIV-specific facility, whereby participants perceived benefits in domains of health and disability. However, challenges transitioning to independent exercise remain. Group-based PT-led exercise programmes may facilitate engagement in exercise among adults living with HIV and complex multimorbidity.
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