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This article belongs to the Special Issue Dietary Patterns, Dietary Indices for Colorectal Cancer, Mortality and the Related Disease. ; Cancer mortality rates are undergoing a global downward trend; however, metastasis and relapse after surgery and adjuvant treatments still correlate with poor prognosis and represent the most significant challenges in the treatment of this disease. Advances in genomics, metabolomics, and proteomics are improving our understanding regarding cancer metabolic diversity, resulting in detailed classifications of tumors and raising the effectiveness of precision medicine. Likewise, the growing knowledge of interactions between nutrients and the expression of certain genes could lead to cancer therapies based on precision nutrition strategies. This review aims to identify the recent advances in the knowledge of the mechanistic role of bioactive phytochemicals in foodstuffs in tumor progression, metastasis, and chemo-resistance in order to assess their potential use in precision nutrition therapies targeting relapse in lung, breast, colon, and prostate cancer, and leukemia. A considerable number of bioactive phytochemicals in foodstuffs were identified in the literature with proven effects modulating tumor growth, progression, and metastasis. In addition, the use of foodstuffs in cancer, and specifically in relapse therapies, is being reinforced by the development of different formulations that significantly increase the therapeutic efficiency of these products. This can open the possibility for testing combinations of bioactive phytochemicals with cancer relapse treatments as a potential prevention strategy. ; This research is part of the work plan of Project AGL2016-76736-C3 supported by the Spanish Ministerio de Ciencia, Innovación y Universidades; Project P2018/BAA-4343-ALIBIRD2020-CM supported by the Regional Government of Comunidad de Madrid (V PRICYT). ; Peer reviewed

In addition to oncogenic drivers, signaling nodes can critically modulate cancer-related cellular networks to strength tumor hallmarks. We identify G-protein-coupled receptor kinase 2 (GRK2) as a relevant player in breast cancer. GRK2 is up-regulated in breast cancer cell lines, in spontaneous tumors in mice, and in a proportion of invasive ductal carcinoma patients. Increased GRK2 functionality promotes the phosphorylation and activation of the Histone Deacetylase 6 (HDAC6) leading to de-acetylation of the Prolyl Isomerase Pin1, a central modulator of tumor progression, thereby enhancing its stability and functional interaction with key mitotic regulators. Interestingly, a correlation between GRK2 expression and Pin1 levels and de-acetylation status is detected in breast cancer patients. Activation of the HDAC6-Pin1 axis underlies the positive effects of GRK2 on promoting growth factor signaling, cellular proliferation and anchorage-independent growth in both luminal and basal breast cancer cells. Enhanced GRK2 levels promote tumor growth in mice, whereas GRK2 down-modulation sensitizes cells to therapeutic drugs and abrogates tumor formation. Our data suggest that GRK2 acts as an important onco-modulator by strengthening the functionality of key players in breast tumorigenesis such as HDAC6 and Pin1. ; Our laboratory is funded by grants from Ministerio de Economía y Competitividad (SAF2011-23800 and SAF2014-55511R), the European Union (H2020-MSCA Programme, Grant agreement 64183-ONCORNET), The Cardiovascular Network of Ministerio Sanidad y Consumo-Instituto Carlos III (RD12/0042/0012), Comunidad de Madrid (S-2010/BMD-2332) to F.M and Instituto Carlos III (PI11/00859, PI14-00435, PIE-13-00041), Fundación Ramón Areces and Fundación Rodríguez Pascual to P.P. Dr.MartaMendiola is supported by a postdoctoral research contract of Fondo de Investigación Sanitaria (FIS) ('Sara Borrell' Program), Instituto de Salud Carlos III