Oncogene
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DNA damage is a deleterious threat, but occurs daily in all types of cells. In response to DNA damage, poly(ADP-ribosyl)ation, a unique post-translational modification, is immediately catalyzed by poly(ADP-ribose) polymerases (PARPs) at DNA lesions, which facilitates DNA damage repair. ⋯ Moreover, PARP inhibitors are emerging as anti-cancer drugs in phase III clinical trials for BRCA-deficient tumors. In this review, we discuss recent findings on poly(ADP-ribosyl)ation in DNA damage response as well as the molecular mechanism by which PARP inhibitors selectively kill tumor cells with BRCA mutations.
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The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise. Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK), has received widespread attention. ⋯ Furthermore, we summarize recent laboratory as well as clinical findings relating to the first cases of Ibrutinib resistance. Finally, we address combination strategies with Ibrutinib, and attempt to extrapolate its current status to the near future in the clinic.
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For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment choices for these patients have expanded to include abiraterone acetate, cabazitaxel and enzalutamide. ⋯ This review will discuss the transformation of the post-docetaxel space in mCRPC, highlighting the spectrum of newly approved agents in this setting in the USA and the European Union, as well as summarizing treatments with non-chemotherapeutic mechanisms of action that have demonstrated promising results in recent phase 3 trials. Lastly, this review will address the potential of combinatorial regimens in mCRPC, including the pairing of novel immunotherapeutic approaches with chemotherapy, radiotherapy or androgen ablation.
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Regular use of aspirin reduces incidence and mortality of various cancers, including colorectal cancer. Anticancer effect of aspirin represents one of the 'Provocative Questions' in cancer research. Experimental and clinical studies support a carcinogenic role for PTGS2 (cyclooxygenase-2), which is an important enzymatic mediator of inflammation, and a target of aspirin. ⋯ However, genomic, epigenomic and molecular pathology testings (for example, analyses for microsatellite instability, MLH1 promoter CpG island methylation, and KRAS and BRAF mutations in colorectal tumors) are becoming routine clinical practices. In order for integrative molecular and population science to be routine practice, we must first reform education curricula by integrating both population and molecular biological sciences. As consequences, next-generation hybrid molecular biological and population scientists can advance science, moving closer to personalized precision medicine and health care.
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Efficient metastasis is believed as the result of multiple genetic, epigenetic and/or post-translational events in the lifetime of a carcinoma. At the genetic level, these events may be categorized into those that occur during carcinogenesis, and those that occur during subclonal evolution. This review summarizes current knowledge of the genetics of pancreatic cancer from its initiation within a normal cell until the time that is has disseminated to distant organs, many features of which can be extrapolated to other solid tumor types. The implications of these findings to personalize genome analyses of an individual patient's tumor are also discussed.