Publications by authors named "Constanza Tapia Contreras"

Article Synopsis
  • * Direct KRAS inhibitors are showing promise in clinical trials, but resistance to treatment is a concern, prompting the search for combination therapies.
  • * Unbiased drug screening identified effective combinations involving SOS1 inhibitors, PTPN11/SHP2 inhibitors, and multi-kinase inhibitors, validated using a unique KRAS-mutated patient-derived organoid model.
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Article Synopsis
  • Cancer cells adapt to various stresses, including those from treatments, through metabolic adaptability, focusing on the energy sensor AMP-activated protein kinase (AMPK).
  • In pancreatic ductal adenocarcinoma (PDAC), high levels of AMPK expression and activity were observed, leading to the identification of PF-3758309 as a potential AMPK inhibitor through drug repurposing.
  • PF-3758309 not only demonstrates pre-clinical effectiveness in PDAC models but also helps sensitizes cancer cells to ferroptosis inducers, paving the way for AMPK-targeted therapies in combination treatments for this type of cancer.
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The sperm flagellum is essential for the transport of the genetic material toward the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e.

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The wound healing response of fibroblasts critically depends on the primary cilium, a sensory organelle protruding into the environment and comprising a stable axonemal structure. A characteristic marker for primary cilia is acetylation of axonemal tubulin. Although formation of primary cilia is under cell cycle control, the environmental cues affecting ciliation are not fully understood.

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Development of spermatozoa requires remodelling and formation of particular structures. In elongating spermatids, the transient microtubular manchette contributes to the formation of the head-tail coupling apparatus (HTCA) and the sperm tail. The HTCA derives from the centrosome in that the proximal centriole inserts into the nuclear indentation and the distal centriole gives rise to the sperm flagellum.

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Terminal differentiation of male germ cells into functional spermatozoa requires shaping and condensation of the nucleus as well as the formation of sperm-specific structures. A transient microtubular structure, the manchette, is mandatory for sperm head shaping and the development of the connecting piece and the sperm tail. The connecting piece or head-to-tail coupling apparatus (HTCA) mediates the tight linkage of sperm head and tail causing decapitation and infertility when faulty.

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The centrosome, as the main microtubule-organizing center, safeguards chromosome segregation by supporting the bipolar spindle. Centrosome aberrations are causally related to chromosome segregation disorders, both characterizing cancer cells. Thus, a restriction to only having one centrosome per cell and cell cycle-dependent duplication of the centrosome is mandatory.

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