Several functional signaling pathways submodules that control the cancer cell proliferation participate simultaneously in the cell growth, cell survival, cell differentiation, intracellular senescence and death programs, and in appropriate interaction with angiogenesis, cell microenvironment regulation and immunologic system signaling pathways. Selective targeted drugs of hub molecules may optimize patient's treatment efficacy, such as de use of CDK4/6 inhibitors that improve the outcomes of patients with HR+ breast cancer (BC) [1].

Physical processes play important roles in controlling eutrophication and oligotrophication. In stratified lakes, internal waves (IW) can cause vertical transport of heat and nutrients without breaking the stratification, through boundary mixing (BM) events. Such is the case in tropical Valle de Bravo (VB) lake, where strong diurnal winds drive IW, BM and hypolimnetic warming during stratification periods. We monitored VB during 18 years (2001-2018) when important water-level fluctuations (WLF) occurred, affecting mixing and nutrient flux. Mean hypolimnetic temperature increase (0.06–1.04°C month-1) occurred in all the stratifications monitored. We analyzed temperature distributions and modeled the hypolimnion heat budget to assess vertical mixing between layers (26,618–140,526 m-3h-1), vertical diffusivity coefficient KZ (6.2x10-7–3.3x10-6 m2s-1) and vertical nutrient entrainment to epilimnion on monthly scale. Stability also varied as a function of WLF. Nutrient flux to the epilimnion ranged 0.36–5.99 mg m-2d-1 for soluble reactive phosphorus (SRP) and 5.8–97.1 mg m-2d-1 for dissolved inorganic nitrogen (DIN). During low water-level years, vertical nutrient fluxes increase and can account for up to >40% of the total external nutrients load to the lake. Vertical mixing changes with WLF affect nutrient recycling, their flux to sediments, metabolic balance and planktonic composition of VB.