Triple-negative breast cancer (TNBC) has been clinically difficult to manage because of tumor aggressiveness, cellular and histological heterogeneity, and molecular mechanisms’ complexity. All this in turn leads us to evaluate that tumor biological behavior is not yet fully understood. Additionally, the heterogeneity of tumor cells represents a great biomedicine challenge in terms of the complex molecular—genetical-transcriptional and epigenetical—mechanisms, which have not been fully elucidated on human solid tumors.Recently, human breast cancer, but specifically TNBC is under basic and clinical-oncology research in the discovery of new molecular biomarkers and/or therapeutic targets to improve treatment responses, as well as for seeking algorithms for patient stratification, seeking a positive impact in clinical-oncology outcomes and life quality on breast cancer patients.In this sense, important knowledge is emerging regarding several cancer molecular aberrations, including higher genetic mutational rates, LOH, CNV, chromosomal, and epigenetic alterations, as well as transcriptome aberrations in terms of the total gene-coding ribonucleic acids (RNAs), known as mRNAs, as well as non-coding RNA (ncRNA) sequences. In this regard, novel investigation fields have included microRNAs (miRNAs), as well as long ncRNAs (lncRNAs), which have been importantly related and are likely involved in the induction, promotion, progression, and/or clinical therapeutic response trackers of TNBC. Based on this, in general terms according with the five functional archetype classification, the lncRNAs may be involved in the regulation of several molecular mechanisms which include genetic expression, epigenetic, transcriptional, and/or post-transcriptional mechanisms, which are nowadays not totally understood.Here, we have reviewed the main dis-regulated and functionally non- and well-characterized lncRNAs and their likely involvement, from a molecular enrichment and mechanistic point of view, as tumor biomarkers for breast cancer and its specific histological subtype, TNBC. In reference to the abovementioned, it has been described that some lncRNA expression profiles correspond or are associated with the TNBC histological subtype, potentially granting their use for TNBC malignant progression, diagnosis, tumor clinical stage, and likely therapy. Based on this, lncRNAs have been proposed as potential biomarkers which might represent potential predictive tools in the differentiated breast carcinomas versus TNBC malignant disease. Finally, elucidation of the specific or multi-functional archetypal of lncRNAs in breast cancer and TNBC could be fundamental, as these molecular intermediary-regulator “lncRNAs” are widely involved in the genome expression, epigenome regulation, and transcriptional and post-transcriptional tumor biology, which in turn will probably represent a new prospect in clinical and/or therapeutic molecular targets for the oncological management of breast carcinomas in general and also for TNBC patients.

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Triple negative breast cancer (TNBC) is an aggressive type of cancer that accounts for ~23% of breast tumors in Mexico. In an attempt to understand in an improved way the behavior of TNBC, throughout the years, gene expression in these tumors has been studied. Lehman et al identified 6 subtypes of gene expression in TNBC with distinct characteristics. In the present study, it was aimed to assess clinical, pathological and prognostic characteristics of TNBC in a Mexican-based cohort. A total of 55 patients diagnosed with TNBC at Mexico's National Institute of Cancer (INCan) were included. Tumor needle biopsy samples were obtained and subjected to microarray analysis. Patients were thus classified into one of the 6 TNBC molecular subtypes. The prognostic, clinical and pathological information of patients was obtained, and differences across molecular subtypes were sought. Out of the 55 included patients, the following subtypes were identified: 9 basal-like-1, 11 basal-like-2 (BSL2), 16 immunomodulatory (IM), 12 mesenchymal, 6 androgen receptor-like and 1 mesenchymal stem-like. Mean follow-up time was 47.1 months. The IM molecular subtype had the best overall survival (OS) (median OS was not reached). BSL2 had the worst OS (15 months). A complete pathologic response to neoadjuvant chemotherapy was obtained more often in the IM subtype (P=0.032). No significant associations were found between any of the clinical or pathological characteristics and the TNBC molecular subtypes. The results obtained from the present study should be considered when seeking to implement a clinical-molecular model for TNBC patient care, particularly in Hispanic-based populations, as they have been frequently underrepresented in clinical studies assessing TNBC molecular subtypes.

Rectal cancer is considered a major health issue in several countries that present advanced and metastatic stages and a limited response to standard treatments. Though the antineoplasic activity of cannabinoids has been documented in several studies, scarce information is available about the effect of these agents in cell lines of rectal cancer. In this work, we explored the antiproliferative effects of cannabinoid receptor agonists in rectal tumor cells. The effects of the three agonists anandamide, methanandamide and CP55940 were evaluated in the SW837 rectal tumor cell line. The three agents tested showed time and concentration dependent effects on cell viability, induction of cell death and morphological changes. The three agonists were effective to induce late apoptosis and necrosis and internucleosomal DNA fragmentation. In addition, we evaluated for the first time the patterns of CB1 and CB2 cannabinoid receptor expression in SW837. Though some differences in their effects were found, our data support the concept that these agents mostly share common antiproliferative/cell death mechanisms. Our results also confirm the antineoplasic potential of cannabinoids receptor agonists against rectal cancer, and suggest the design of cannabinoid based coadjutant therapies at the clinical level. Citation Format: Alette Ortega Gómez, Pedro Luna-Merlos, Victor Manuel García Hernández, Abelardo Meneses García, Horacio Astudillo- de la Vega, Eric Alejandro García López, Abel Santamaría Del Angel, Erika Betzabé Ruiz García. Antiproliferative effect of cannabinoid receptor agonists on rectal cancer lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1903.