Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

Sequential targeted therapies are the standard of care for patients with metastatic renal cell carcinoma (mRCC). Several drugs are available for patients whose disease progresses while they receive initial tyrosine kinase inhibitor (TKI) therapy; these include nivolumab (an inhibitor of PD-1 receptor), everolimus (an inhibitor of the mechanistic target of rapamycin) or additional TKIs. Until now, there has been no clinical evidence to support the use of one strategy versus another, so investigators and physicians rely on experience, judgement and findings from molecular analyses to select the appropriate treatment. However, with the arrival of nivolumab and cabozantinib that provide an overall survival higher than other alternative treatments, therapeutic strategies may have changed. Here, we discuss findings from preclinical and clinical studies that might help clinicians to choose the optimal treatment approach for patients with mRCC who progress to initial therapy.

Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial. Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy. In addition, we outline the management of adverse events associated with these agents, highlighting the importance of switching to an alternative mechanism of action to overcome resistance to TKI and to decrease cumulative toxicity associated with sequential treatments of the same type. Expert commentary: The choice of subsequent therapy after progression to first-line is not clear. Although the new drugs cabozantinib and nivolumab have shown to be superior that everolimus, still it is unknown which patients may benefit from these therapies in second-line, so treatment should be personalized to each patient and should consider approaches with different mechanisms of action.

El carcinoma de células basales de la vulva es una lesión muy rara, y ocupa el cuarto lugar en el total de los tumores malignos de la vulva atendidos en el Instituto Nacional de Enfermedades Neoplásicas de Lima, con una incidencia de 2,7 por ciento. El simple Vulvectomía es la más adecuada por parte de la terapia cuando el carcinoma de células basales está presente por sí mismo, es decir, puro. La vulvectomía radical y disección de los ganglios regionales bilaterales deben practicarse en todos los casos de lesiones basales células escamosas.

El problema de la cirugía radical en el cáncer ginecológico fue presentado por el Dr. Luis Esteves en relación a la casuístico y experiencia en el Dpto. de Ginecología del I.N .E.N. del cual es jefe, de 1952 a 1959; tiempo después del cual creía un deber informar a esta sociedad y a los colegas ginecólogos en general, de la labor cumplida en ese período de 7 años. Hizo presente que el trabajo se refiere exclusivamente al tratamiento quirúrgico, dejando constancia que la cirugía radical y ultrarradical del cáncer pélvico en la mujer fue introducida en nuestro medio, por él, con la cooperación del Dr. Castellano en el año 1952. Igualmente dejó constancia, también, que en otros centros, especialmente en el servicio de ginecología del Hospital Loayza Pab. 5 II, con posterioridad otros ginecólogos cultivan en forma limitada algunos aspectos de dicho cirugía radical.