Rho GTPases are key molecular switches controlling the transduction of external signals to cytoplasmic and nuclear effectors. In the last few years, the development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rho GTPases in cancer. The aim of the present review is to describe the cellular functions regulated by these proteins with focus in deregulated signals present in malignant tumors. Finally, we describe the state of the art in search of different experimental therapeutic strategies with Rho GTPases as molecular targets.

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Telomeropathies involve a wide variety of infrequent genetic diseases caused by mutations in the telomerase maintenance mechanism or the DNA damage response (DDR) system. They are considered a family of rare diseases that often share causes, molecular mechanisms and symptoms. Generally, these diseases are not diagnosed until the symptoms are advanced, diminishing the survival time of patients. Although several related syndromes may still be unrecognized this work describes those that are known, highlighting that because they are rare diseases, physicians should be trained in their early diagnosis. The etiology and diagnosis are discussed for each telomeropathy and the treatments when available, along with a new classification of this group of diseases. Ethical and legal issues related to this group of diseases are also considered.

Malignant gliomas are the most common primary central nervous system tumor in adults. Despite current therapeutics, these tumors are associated with poor prognosis and a median survival of 16 to 19 months. This highlights the need for innovative treatments for this incurable disease. Rac1 has long been associated with tumor progression and plays a key role in glioma’s infiltrative and invasive nature. The aim of this study is to evaluate the 1A-116 molecule, a Rac1 inhibitor, as targeted therapy for this aggressive disease. We found that targeting Rac1 inhibits cell proliferation and cell cycle progression using different in vitro human glioblastoma models. Additionally, we evaluated 1A-116 in vivo, showing a favorable toxicological profile. Using in silico tools, 1A-116 is also predicted to penetrate the blood–brain barrier and present a favorable metabolic fate. In line with these results, 1A-116 i.p daily treatment resulted in a dose-dependent antitumor effect in an orthotopic IDH-wt glioma model. Altogether, our study provides a strong potential for clinical translation of 1A-116 as a signal transduction-based precision therapy for glioma and also increases the evidence of Rac1 as a key molecular target.