Clinical and Translational Oncology

Breast cancer (BC) is one of the most prevalent types of cancer in women. Despite advancement in early detection and efficient treatment, recurrence and metastasis continue to pose a significant risk to the life of BC patients. Brain metastasis (BM) reported in 17–20 percent of BC patients is considered as a major cause of mortality and morbidity in these patients. BM includes various steps from primary breast tumor to secondary tumor formation. Various steps involved are primary tumor formation, angiogenesis, invasion, extravasation, and brain colonization. Genes involved in different pathways have been reported to be associated with BC cells metastasizing to the brain. ADAM8 gene, EN1 transcription factor, WNT, and VEGF signaling pathway have been associated with primary breast tumor; MMP1, COX2, XCR4, PI3k/Akt, ERK and MAPK pathways in angiogenesis; Noth, CD44, Zo-1, CEMIP, S0X2 and OLIG2 are involved in invasion, extravasation and colonization, respectively. In addition, the blood–brain barrier is also a key factor in BM. Dysregulation of cell junctions, tumor microenvironment and loss of function of microglia leads to BBB disruption ultimately resulting in BM. Various therapeutic strategies are currently used to control the BM in BC. Oncolytic virus therapy, immune checkpoint inhibitors, mTOR-PI3k inhibitors and immunotherapy have been developed to target various genes involved in BM in BC. In addition, RNA interference (RNAi) and CRISPR/Cas9 are novel interventions in the field of BCBM where research to validate these and clinical trials are being carried out. Gaining a better knowledge of metastasis biology is critical for establishing better treatment methods and attaining long-term therapeutic efficacies against BC. The current review has been compiled with an aim to evaluate the role of various genes and signaling pathways involved in multiple steps of BM in BC. The therapeutic strategies being used currently and the novel ones being explored to control BM in BC have also been discussed at length.

Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited. AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m2 plus paclitaxel 150 mg/m2, on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients. Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9–82.0 %) and 89 % (95 % CI 80.3–95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) ≥2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %). Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response.

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

Metastasis to the thyroid occur infrequently. The overall incidence in autopsy series vary from 0–5% in unselected cases to 24% in patients with a known malignancy. They usually occur when there are another metastases, sometimes many years after diagnosis of the original primary tumour. We present the case of a woman with dysphagia and dysphonia due to a thyroid mass as first manifestation of a metastatic breast cancer.

Aberrations in the PI3K signaling pathway are frequently observed in patients with breast cancer. Because of that, PI3K inhibitors are attractive options for the treatment of breast cancer because PI3K is the most proximal component of the pathway other than receptor tyrosine kinases. Buparlisib is a potent and highly specific oral pan-class I PI3K inhibitor, which is currently under investigation in patients with breast cancer. In this article, we describe the PI3K signaling pathway, the prognostic value of PI3K pathway mutations, as well as the mechanism of action of buparlisib. Lastly, we discuss preliminary results of preclinical and clinical studies showing the efficacy and safety profile of this agent in breast cancer patients.

The aim of this research was to find the sonographic features of primary tumor as independent predictive factors for lymph node metastasis in papillary thyroid carcinoma. To facilitate the research, 514 patients with papillary thyroid carcinoma were divided into solitary and multifocal groups. In solitary group, thyroid lesions were divided into several subgroups by size, border, margin, echogenicity, echohomogeneity, calcification, vascularization, location, stiffness and Hashimoto’s thyroiditis (HT) conditions. Then, univariable and multivariable analyses were performed to find the sonographic features of primary tumor as independent predictive factors for lymph node metastasis in papillary thyroid carcinoma. A significant difference of lymph node metastasis rate was found between multifocal and solitary groups (P < 0.05). In univariable analysis, size, vascularization and coexistence of HT were found to be statistically significant factors (P = 0.004, 0.118, 0.016). Multivariable analysis revealed that lymph node metastasis rate was mainly associated with size [odds ratio (OR) = 1.690, 95 % confidence interval (CI) 1.157–2.469] and coexistence of HT (OR = 0.441, 95 % CI 0.219–0.888). Preoperative sonographic features of primary tumor including the number, size and coexistence of HT were independent predictive factors for the state of cervical lymph node metastasis in patients with papillary thyroid carcinoma.

El cáncer colorrectal es uno de los tumores mejor conocidos de todas las enfermedades malignas en términos genéticos y/o moleculares. Su conocimiento y su relación con el pronóstico puede tener importantes implicaciones, fundamentalmente en el diseño de estrategias quirúrgicas y de quimiorradioterapia adyuvante. Sin embargo, aún desconocemos el verdadero significado pronóstico de todos los factores hasta ahora estudiados. Es este trabajo hemos revisado la literatura acerca del papel especifico de los marcadores moleculares en cáncer colorrectal y su probable respuesta al tratamiento.