Breast cancer is a leading type of cancer among women in India as well as worldwide. According to the WHO 2015 report, it has been anticipated that there would be a twofold rise in the death due to breast cancer among women. The heterogeneous property of breast carcinoma has been suggested to be linked with dedicated set of communication and signaling pathway with their surroundings, which culminate into progression and development of the cancer. Among the plethora of communication tools in the hand of breast carcinoma cells is the recently appreciated exocytosis of the tightly packed short non-coding RNA molecules, predominantly the microRNAs (miRNAs). Recent studies suggest that miRNAs may work as courier messengers to participate in endocrine and paracrine signaling to facilitate information transfer between breast carcinoma and their neighboring cells. Evidence suggests that breast tumor cells communicate via packaged miRNAs in the tumor-released microvesicles, which enrich the tumor microenvironment. There is a strong view that dissecting out the mechanistic and regulatory aspects of miRNA export and role may uncover many prospects for overcoming the signaling defects and thereby controlling aberrant cell division. The detection of circulating miRNAs associated with breast carcinoma can also be used as biomarkers for early diagnosis. This review article is an attempt to provide updated knowledge on implications of short RNAs and their transport in the breast cancer pathophysiology.

Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma.

Several approaches including chemotherapy and radiation therapies are being at the forefront to treat various types of cancer including cervical cancer. However, the success and failure of genotoxic based therapy is attributed to aberrant ability of carcin oma to patch up genomic breaks. Here, we have used cisplatin as a genotoxic drug model and HeLa as in vitro carcinoma model due to less responsiveness and resistance of HeLa against cisplatin. Here, attempts are made to investigate the effects of DNA double strand break inhibitor KU-55933 against the cisplatin cell growth and cytotoxicity. Following experiments namely in vitro plasmid DNA metabolizing, Trypan blue dye exclusion, M TT, and PI based Flow cytometery PI assays were conducted to study cell growth and cytotoxicity effects. Based on the cell viability and PI based staining data, results remarked that KU -55933 combined with cisplatin could bring convincing cell growth arrest in HeLa. The reduction in HeLa proliferation was noticed from 70% to 30% in case of KU-55933 added with cisplatin over cisplatin alone. However, we noticed none apoptosis based cell cytotoxicity in case of cisplatin alone or combined with the inhibitors. We also observed significant DNA instability in case of KU-55933 treated HeLa lysates added to plasmid DNA substrate over HeLa lysate without KU-55933 treatment. In conclusion, KU-55933 can potentiate low dose of cisplatin response against HeLa. The effect of KU-55933 may not be attributed due to its enhancing the apoptosis way, rather than through cell growth arrest mechanism due to extensive DNA breaks.

Temozolomide (TMZ) is approved against certain tumors, but substantial evidences are scarce to demonstrate TMZ as single-strand DNA break agent and reasons behind lack of responses in carcinoma. Plasmid and genomic DNA included as a substrate during assessment of in vitro single-strand break potential of TMZ. Cell based assay was performed to assess DNA damaging activity and cytotoxicity in HeLa. Further, authors tried to evaluate DNA damage and overall cytotoxicity in HeLa using Trypan blue dye exclusion and apoptotic DNA fragmentation assays. Data indicate that TMZ can generate extensive single-strand break on different DNA substrate. A DNA ligase inhibitor L189 appears to plays synergistic role in TMZ ability to decrease cell proliferation in HeLa and some extent of cytotoxicity. However, authors noticed none apoptotic DNA fragments due to toxicity effects of TMZ alone or combined TMZ plus L189. Based on our observations, findings support combined use of TMZ and L189 inhibitor to enhance responsiveness in HeLa possibly by decreasing cellular growth instead of apoptotic cell death pathway.

Treating breast carcinoma gets tedious due to its invasive molecular subtypes and their various molecular genotypes. Depending upon genotype and phenotype of breast tumor types, they manipulate their survival arms in the form of DNA repair protein player including base excision repair (BER) pathway. Currently, avenues to treat breast cancer ate genotoxic drugs inflicting inter and intra-strand cross links, base modification and changes in the genome combined with inhibitors of BER pathway. This review summarizes the updated information on the relevance of BER response in breast carcinoma phenotypes and their potential therapeutic interference in the last decade.

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NK) withdrew their article in the year 2016-2017 after acceptance, due to non-payment of APC charges. Unfortunately, a technical error in 2019 led to the article's publication online. The production team of this journal takes full responsibility and apologizes for the technical error that resulted in the publication of this article. The article "In vitro single-strand DNA damage and cancer cell cytotoxicity of temozolomide (

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