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Background. The treatment for patients with high-grade gliomas includes radiation therapy and temozolomide. However, some patients do not respond to temozolomide because they have a methylation reversal mechanism through the enzyme O6-methylguanine-DNA-methyltransferase. This biomarker has been used as a prognostic factor in patients receiving treatment with temozolomide. However, not all patients respond in the same way, which suggests the existence of other genes involved in resistance to temozolomide. Materials and Methods. A group of 31 patients with high-grade gliomas was recruited and were clinically, image pattern, and pathologically characterized. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment. Results. The genes related to the second relapse of patients with high-grade glioma after the use of temozolomide according to Stupp protocol and metronomic dose were PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. Considering the results obtained, we suggest that the mutations in the four genes and the methylation of the gene promoter that codes for MGMT protein could be related to the clinical evolution of patients with high-grade gliomas and its response to treatment with temozolomide.

Background: Locally advanced triple negative breast cancer (laTNBC) patient's exhibits resistance to neoadjuvant chemotherapy (NC) and poor survival. Distinct therapeutic combinations have been used to reduce high mortality. Recently, novel regimens of NC for laTNBC have achieved pathological complete response (pCR) rates of 10-50%. Evaluation of pCR during oncologic treatment is decisive to identify those patients that response or not response to NC. MicroRNAs (miRNAs) are small non-coding RNAs that represent novel and potential predictive biomarkers useful to identify the patients who will get pCR in cancer. Methods: Thirty-five patients diagnosed with laTNBC, were invited to participate in this study and enrolled after they signed an informed consent. The 22 patients with pCR and 13 patients without pCR received the experimental NC fluorouracil, adriamycin, cyclophosphamide, cisplatin, paclitaxel (FAC--CDDP/paclitaxel). MiRNA expression profiling was evaluated for 754 miRNAs. A discovery cohort (n=10 pCR and n=8 no-pCR) and a validation cohort (n=12 pCR and n=5 no-pCR). Bioinformatics analysis revealed the affected cellular pathways in pCR group. After a median clinical follow-up of 60 months, statistical analysis was performed to identify miRNAs that could discriminate pCR from no-pCR by using FAC--CDDP/paclitaxel. Results: MiRNAs expression profiling identified 11 miRNAs that showed significant differences between pCR and no-pCR (p<0.05 and fold change >1.5) groups. Eight miRNAs (miR-9-3p, -30a-3p, -135b, -135b*, -380-5p, -941, -652 and miR-181c*) were upregulated and three miRNAs (miR-770-5p, -584 and miR-143) were downregulated in pCR patients. The altered cellular pathways for the set of miRNAs were PI3K/AKT, FoxO, Ras and ERBB (p<0.05). Four differentially expressed miRNAs (miR-770-5p, miR-143-5p, miR-30a-3p, miR-9-3p) were confirmed in the validation phase. Expression of these miRNAs above the median level was a significant predictor of pCR to experimental NC in laTNBC patients (p<0.001). Conclusions: These four validated miRNAs could be used as predictors of pCR in response to FAC---CDDP/Paclitaxel treatment in laTNBC patients. Citation Format: Vázquez RG, Camarillo CL, Marchau LM, García ER, Miranda AA, Martínez HM, Parra AC, De la Vega HA, Barrios AG, Cuevas SR. A microRNA signature associated with pathological complete response to a novel neoadjuvant therapy regimen in triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-11.

e20019 Background: The number of agents active in patients with metastatic melanoma is limited and cure is not an objective for treatment at this stage, so that clinical benefit in these patients is the most important. The aim of the study was to evaluate the efficacy and safety of combination regimen consisting of paclitaxel and carboplatin as second-line chemotherapy, in patients with MM. Based on reports of responses to PC, 17 patients with MM was treated at the National Cancer Institute of Mexico. Methods: We evaluated retrospectively the combination of PC in patients with MM. Data regarding patient characteristics and outcomes were abstracted from medical records of NCI of Mexico from 01/05 to 12/08. The regimen was weekly paclitaxel (at a dose of 80 mg/m2) received on days 1, 8, and 15 of a 21-day cycle and carboplatin (AUC 5) on day 1. Response evaluation was using RECIST and toxicity was according to National Cancer Institute Common Toxicity Criteria. This study was approved by the hospital ethics committee. Results: Seventeen patients with MM were treated with PC. All patients were previously treated (and failed) with dacarbazine (DTIC). Sixteen were assessable for response with three cycles of chemotherapy and seventeen for toxicity. One patient was deemed to be ineligible because they presented severe hypersensitivity reaction to paclitaxel at beginning. Objective partial response were obtained in 4 patients (25%); 8 stable disease (50%) at least four months. No patient had a complete response to therapy. Progression disease was in 4 patients (25%). In 12 (75%) we noted clinical benefit. The median time to disease progression for the entire group was 4.2 months (range, 1–11 mos), with a median overall survival of 8.1 months (range, 5.6–10.5 mos). The toxicity grade 3 reported was thrombocytopenic in 2 patients (11%) and anemia in one patient (6%). Additional patients had reversible toxicities grade 3 including alopecia, nausea and fatigue; 2 of them presented moderate hypersensitivity reactions to paclitaxel. No toxic death was noted. Conclusions: The PC combination appears to be safety and well tolerated in second line chemotherapy in MM, however we need more patients to demonstrate a true clinical benefit, we outcomes are according with other clinical reports. No significant financial relationships to disclose.