Track topics on Twitter Track topics that are important to you
The development of drug-resistance by neoplastic cells is recognized as a major cause of targeted therapy failure and disease progression. The mechanistic (previously mammalian) target of rapamycin (mTOR) is a highly conserved Ser/Thr kinase that acts as the catalytic subunit of two structurally and functionally distinct large multiprotein complexes, referred to as mTOR complex 1 (mTORC1) and mTORC2. Both mTORC1 and mTORC2 play key roles in a variety of healthy cell types/tissues by regulating physiological anabolic and catabolic processes in response to external cues. However, a body of evidence identified aberrant activation of mTOR signaling as a common event in many human tumors. Therefore, mTOR is an attractive target for therapeutic targeting in cancer and this fact has driven the development of numerous mTOR inhibitors, several of which have progressed to clinical trials. Nevertheless, mTOR inhibitors have met with a very limited success as anticancer therapeutics. Among other reasons, this failure was initially ascribed to the activation of several compensatory signaling pathways that dampen the efficacy of mTOR inhibitors. The discovery of these regulatory feedback mechanisms greatly contributed to a better understanding of cancer cell resistance to mTOR targeting agents. However, over the last few years, other mechanisms of resistance have emerged, including epigenetic alterations, compensatory metabolism rewiring and the occurrence of mTOR mutations. In this article, we provide the reader with an updated overview of the mechanisms that could explain resistance of cancer cells to the various classes of mTOR inhibitors.
This article was published in the following journal.
Name: Biochimica et biophysica acta. Molecular cell research
The antibiotic ciprofloxacin is used extensively to treat a wide range of infections caused by the opportunistic pathogen Pseudomonas aeruginosa. Due to its extensive use, the proportion of ciprofloxa...
This review highlights advances in mechanisms of allergic disease, particularly type 2 innate lymphoid cells; T2 lymphocytes; B cells; dendritic cells: microbiome and barrier function; eosinophils, ma...
Inhibitors of poly(ADP-ribose) polymerase (PARPi) have entered the clinic for the treatment of patients with cancers that lack homology-directed DNA repair, but drug resistance remains a clinical hurd...
Bruton's tyrosine kinase (BTK) is a key mediator of BCR-dependent cell growth signaling and a clinically effective therapeutic target in mantle cell lymphoma (MCL). The molecular impact of BTK inhibit...
Accumulating evidence suggests that human infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, indicating that NTM disease is no longer uncommon in many countries. As a res...
In the context of Candida yeast infections, a large number of studies have been published over the past two decades specifying the molecular mechanisms of antifungal resistance in differen...
There is a clear need for novel effective agents in castration-resistant prostate cancer (CRPC), an entity previously referred to as "androgen-insensitive" or "hormone-refractory" prostate...
The underlying hypothesis of the synergistic activity of octreotide and everolimus is based on the combination of a) a direct action of everolimus over mTOR (mammalian target of rapamycin)...
- According to Martin F et al, AKT is highly phosphorylated in phenochromocytoma but not in benign adrenocortical tumors. - In nonfunctioning carcinoid, the PI3K/AKT/mTOR pathway...
Endometrial cancer is the most common malignancy of the female reproductive tract. The majority of patients with endometrial cancer are diagnosed at an early stage and cured with surgery ...
An adaptor protein, consisting of seven WD REPEATS along its length, that functions as a component of the MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1 and MTORC2 COMPLEX. It interacts directly with MTOR to enhance its kinase activity and stabilizes the MTOR-RPTOR PROTEIN interaction in nutrient-poor conditions, favoring RPTOR inhibition of MTOR activity.
The capacity of an organism to defend itself against pathological processes or the agents of those processes. This most often involves innate immunity whereby the organism responds to pathogens in a generic way. The term disease resistance is used most frequently when referring to plants.
Cytosolic signaling adaptor proteins that were initially discovered by their role in the innate immunity (IMMUNITY, INNATE) response of organisms that lack an adaptive immune system. This class of proteins contains three domains, a C-terminal ligand recognition domain, an N-terminal effector-binding domain, and a centrally located nuclear-binding oligomerization domain. Many members of this class contain a C-terminal leucine rich domain which binds to PEPTIDOGLYCAN on the surface of BACTERIA and plays a role in pathogen resistance.
Nonsusceptibility of bacteria to the action of the beta-lactam antibiotics. Mechanisms responsible for beta-lactam resistance may be degradation of antibiotics by BETA-LACTAMASES, failure of antibiotics to penetrate, or low-affinity binding of antibiotics to targets.
The act or fact of grasping the meaning, nature, or importance of; understanding. (American Heritage Dictionary, 4th ed) Includes understanding by a patient or research subject of information disclosed orally or in writing.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...