As these GEITP emails have previously discussed –– whether it’s a bacterial infection being treated with an antibiotic or a malignant tumor being treated with a chemotherapeutic agent –– mutations in the genome (of the bacterium, or the cancer) often occur so that (bacteria or tumor cells) can survive the “environmental adversity”, thereby continuing to thrive. DNA sequence changes as well as epigenetic changes can be involved; this is a fundamental aspect of evolutionary survival: the response of the genome to environmental adversity.
The recurrence of chemoresistance following cancer therapy remains an intractable problem in oncology clinical care and represents a major impediment to decreasing the morbidity and mortality attributable to malignant tumors. To address this issue, scientists have traditionally focused on elucidating the cell-intrinsic mechanisms and mutations that render tumors refractory to classical chemotherapeutic drugs. However, cancers that are located in any organ throughout the body do not develop in isolation. Instead, tumor cells arise in the context of non-malignant cellular and non-cellular components of a tissue, defined as the tumor microenvironment which is currently not well understood. Specific mechanisms of drug resistance clearly can vary significantly between cancer types. The concept that neoplastic cells can choose preexisting or treatment-induced signaling networks to survive therapy –– has emerged as a clear, unifying component of treatment failure.
Intestinal bacteria (i.e. the microbiome) are becoming increasingly appreciated to play major roles in chronic inflammation and carcinogenesis in the intact patient or lab animal. For exxample, chemotherapy failure is a major cause of recurrence and poor prognosis in colorectal cancer patients. Authors [see attached] investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. They found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence following chemotherapy. Furthermore, bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy.
Mechanistically, F. nucleatum targeted TLR4 (toll-like receptor-4) and MYD88 (myeloid differentiation primary response-88) innate immune signaling and specific microRNAs to activate the autophagy (self-destruction of cells) pathway, thereby altering colorectal cancer chemotherapeutic response. Measuring and targeting F. nucleatum and its associated pathway should yield valuable insight into clinical management and may improve colorectal cancer patient outcomes. This topic underscores yet-another means by which a patient’s response to a drug can be altered –– in this case, not directly by genetic or epigenetic differences in the patient’s genome but in the patient’s microbiome.
Cell 2o17; 170: 548–563 & editorial preview pp 411-413
There was another interesting article just published in Nature (attached): “Commensal bacteria make GPCR ligands that mimic human signalling molecules”.
It is “in press,” without volume or page numbers assigned yet. Bacterial metabolites interact with G-protein-coupled receptors (GPCRs), and this interaction regulates gastrointestinal physiology.
Gut microbiomes alter the sensitivity of tumors by a variety of mechanisms. These mechanisms include changes in metabolism, sex hormonal responses, and immune responses. Thank you for sharing the information.