Kirsten Rat Sarcoma (KRAS) gene somatic point mutations is one of the most prominently mutated proto-oncogenes known to date, and accounts for approximately 60% of all colorectal cancer cases. One of the most exciting drug development areas against colorectal cancer is the targeting of undruggable kinases and kinase-substrate molecules, although whether and how they can be integrated with other therapies remains a question. Current clinical trial data have provided supporting evidence on the use of combination treatment involving MEK inhibitors and either one of the PI3K inhibitors for patients with metastatic colorectal cancer to avoid the development of resistance and provide effective therapeutic outcome rather than using a single agent alone. Many clinical trials are also ongoing to evaluate different combinations of these pathway inhibitors in combination with immunotherapy for patients with colorectal cancer whose current palliative treatment options are limited. Nevertheless, continued assessment of these targeted cancer therapies will eventually allow patients with colorectal cancer to be treated using a personalized medicine approach. In this review, the most recent scientific approaches and clinical trials targeting KRAS mutations directly or indirectly for the management of colorectal cancer are discussed.
Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.