Are there any new therapies that target the DDR pathway?
In this sense, a range of new anticancer therapies that target the DDR pathways are being developed to exploit replication stress in cancer cells [2-4]. Information on selecting patients for treatment with agents targeting DDR and mechanisms of resistance can be found by clicking on the links below:
What is DNA damage response (DDR)?
The DNA Damage Response (DDR) is one of the scientific platforms we are focusing on to improve the clinical paradigm in oncology. Our understanding of the role the DDR plays in cancer is enabling us to push our research further to target a broad range of cancers including difficult to treat or aggressive cancers. 1
What are the benefits of DDR Prime essential oils?
Each essential oil contained in DDR Prime has a variety of benefits. Frankincense and Wild Orange have both been shown to promote a healthy response to free radicals.* Clove oil provides powerful antioxidant properties.* Niaouli and Thyme essential oils support cellular immunity and overall cellular health.*
What is DDR Prime cellular complex?
When cellular function is compromised, the normal process of growth and regeneration is altered, negatively impacting all normal and healthy processes. DDR Prime Cellular Complex is a proprietary blend of CPTG Certified Pure Tested Grade™ essential oils combined to support cell health, function, and renewal.*
What is DDR in oncology?
Recent advances in DDR (DNA damage response) inhibitors for cancer therapy. Eur J Med Chem. 2022 Feb 15;230:114109.
What is DDR mutation?
DDR mutation is associated with enriched immune cell infiltration, enhancement of the cancer immunity cycle, elevated TMB, and abundant immune checkpoint expression in the tumor microenvironment.
What is DDR DNA?
The DNA damage response (DDR) involves a complex network of genes responsible for sensing and responding to specific types of DNA damage, encompassing specific machineries mediating DNA repair, cell cycle regulation, replication stress responses and apoptosis.
Is targeted therapy chemotherapy?
Targeted therapy drugs, like other drugs used to treat cancer, are technically considered chemotherapy. But targeted therapy drugs don't work the same way as traditional or standard chemotherapy (chemo) drugs. Targeted drugs zero in on some of the changes that make cancer cells different from normal cells.
How do you repair damaged DNA?
Most damage to DNA is repaired by removal of the damaged bases followed by resynthesis of the excised region. Some lesions in DNA, however, can be repaired by direct reversal of the damage, which may be a more efficient way of dealing with specific types of DNA damage that occur frequently.
How many DDR genes are there?
There are at least 450 genes associated with DDR [1, 2]. Some identified examples of DDR genes known to be involved in cancer are shown in the table below.
What are the consequences of failure in DNA damage repair response?
Failure to repair DNA lesions may result in blockages of transcription and replication, mutagenesis, and/or cellular cytotoxicity. In humans, DNA damage has been shown to be involved in a variety of genetically inherited disorders, in aging, 3 and in carcinogenesis.
What are DDR proteins?
DDR signaling proteins trigger a wide variety of post-translational modifications and assembly of protein complexes that amplify and diversify the DNA damage signal so that the appropriate responses can be initiated, and can include: transcriptional changes, cell cycle checkpoint activation, alternative splicing, ...
How can DNA repair mechanisms be improved?
Higher intensity activities in particular (running, swimming, fast cycling) appeared to be associated with the greatest benefit to DNA repair capacity. Biologically, physical activity may increase DNA repair by inducing expression of enzymes which dispose of harmful oxygen radicals and repair DNA damage .
How successful is targeted therapy?
The success of imatinib for treating CML is striking: the response rate to imatinib treatment is 90% compared with 35% that can be achieved with conventional chemotherapy [4].
What is the survival rate of targeted therapy?
Currently, more and more people are turning to targeted therapy as a form of treatment for cancer, as it is highly effective when compared to chemotherapy. While chemotherapy offers around a 30% success rate, targeted therapy is successful in up to 80% of cases.
How long can you stay on targeted therapy?
People with advanced and metastatic NSCLC that responds to targeted therapies or checkpoint inhibitors now routinely survive for three or four years after diagnosis, Mok says, and a lucky few live substantially longer.
Why is DDR important?
DDR is essential for the activation of repair pathways and cell survival. DDR sensor proteins, which respond to a wide variety of DNA lesions, are key for initiating repair. For DSBs, Ku and MRN represent the major sensor protein complexes.
What is the function of DDR signaling proteins?
DDR signaling proteins trigger a wide variety of post-translational modifications and assembly of protein complexes that amplify and diversify the DNA damage signal so that the appropriate responses can be initiated, and can include: transcriptional changes, cell cycle checkpoint activation, alternative splicing, engagement of DNA repair processes, or in the context of massive damage, activation of cell senescence or apoptotic pathways.
What is PARP inhibitor?
This is exemplified by the approval of poly (ADP-ribose) polymerase (PARP) inhibitors for treating ovarian cancers with mutations in BRCA1/2. In this case, one gene is inactivated by mutation and the other is inactivated by the drug.
What is DNA repair in cancer?
DNA Damage Response and DNA Repair in Cancer. The DNA repair and DNA damage response (DDR) pathway is frequently disrupted in cancer and is one of the hallmarks of cancer. Germline and/or somatic mutations in critical DNA repair/DDR genes cause predisposition to cancer and higher mutational burden in cancers, respectively.
What is NER in biology?
NER is perhaps the most flexible mechanism in terms of the diversity of lesions that are recognized and repaired. The most significant of these lesions are pyrimidine dimers induced by UV light (cyclobutane pyrimidine dimers and 6-4 photoproducts), and other NER substrates include bulky chemical adducts, DNA intra-strand crosslinks, and some forms of oxidative damage. These types of lesions cause both a helical distortion of the DNA duplex and a modification of the DNA chemistry, both of which are hallmark features recognized by NER.
Can DDR inhibitors be used to block DNA?
To enhance therapeutic efficacy, DDR inhibitors can be combined with drugs targeting other DDR proteins or completely different signaling pathways with the goal of blocking multiple pathways that cancer cells rely on for survival.
Can DDR be used as a sensitizer?
As our understanding of the interactions between DNA damage, DDR, and the immune response increases, there may be potential for increasing clinical efficacy of immunotherapies by combining them with DDR inhibitors and/or radiation as sensitizers.
