Photoactivatable prodrugs are a novel method of drug administration because they enter the body in an inactive state before becoming metabolized to an active state. To prevent detrimental side effects caused by certain cancer treatments, photoremovable protecting groups (PPGs) are used to cage the drug, allowing for temporal and spatial control over administration. This control is essential when the goal of the drug is to inhibit a gene. This leads to the question: what are the advantages and effectiveness of photoactivatable prodrugs with respect to cancer?
The first prodrug, defined in 1958 by Adrien Albert, was acetylsalicylic acid, which is hydrolyzed to salicylic acid resulting in more potency and less bodily irritation. Many different ways to design prodrugs have since been discovered such as adding a polar group to a drug to make it solubleA recent addition to the design of prodrugs include photoremovable protecting groups (PPGs). The first recognized instance of PPGs is the development of caged adenosine 5’ triphosphate (ATP) in 1978.
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displayed the ability of Vemurafenib (Figure 1), a current FDA approved drug for use in BRAFV600E mutant cancers, to hold PPGs. The binding of vemurafenib to BRAFV600E is facilitated through hydrogen bonding between protein residues of BRAFV600E (Figure 2) and two specific moities of vemurafenib: 7-azaindole moiety and sulfonamide NH residue. PPGs are bound to these moieties through nucleophilic substitution, creating caged prodrugs (Figure 3) with groups removable by UV light. The addition of these PPGs causes steric hindrance which inhibits the binding of vemurafenib to BRAFV600E,implementing temporal and spatial control of the administration of
Pharmaceuticals have examined and found to ”work by changing the biological functions of the target cells in the body through chemical agents“ (Doweiko, 2015, p. 16). ”Many people in the past have thought that drugs that
Glioblastoma Multiforme (GMB) is the most common form of primary malignant brain tumor in adults. With the current standard therapy, median survival time hovers just over 12 months. This incurable disease is devastating with a median survival time of 6-8 months from time of recurrence (J10). The current standard of therapy at first diagnosis consists of surgery followed by radiotherapy with concommittant and adjuvant chemotherapy using the agent temozolamide (TMZ) (Multiple sources). In 2003, the United States Food and Drug administration approved the Gliadel Wafer (GW) for treatment of newly diagnosed GBM (C3). The monoclonal antibody Bevacizumab (BEV) was first used to treat recurrent GBM in 2005 and has a significant survival benefit for patients with grade IV glioma (E5). Many more promising avenues for new treatment have been and are currently being studied. Such areas include the use of antiepileptic drugs, using Convection-Enhanced Delivery of chemotherapeutic agents, and targeting specific molecular markers and pathways such as the epidermal growth factor receptor (EGFR), O6-methylguanine-DNA-methyltransferase (MGMT), and the PI3K/Akt/mTOR pathway.
Further research on this alternative model could lead to therapies that not only target the properties of the primary tumor but also those of the secondary tumor and save many from the burden of fighting cancer again.
U.S. Congress, Office of Technology Assessment. 1990. Unconventional Cancer Treatments, OTA-H-405. Washington, D.C.: U.S. Government Printing Office.
...ith photodynamic therapy. Neoplastic tissues would take up compounds of photosensitizing agents, and the interaction of light with the photosensitizing agent eventually leads to the production of cytotoxic free radicles[secret]. The advantages of this treatment is that multiple lesions could be treated even though that could take more than one treatment. However, the downside to this treatment is that it is limited only to neoplasms that are at superficial level. Patients might also acquire side effects such as having photosensitization for around 4-6 weeks, or causing tissues to undergo necrosis which sloughs off after some time.[secret] The latter effect would induce pain in patients.
Chemotherapy is the treatment of a tumor with chemical agents to reduce mass or eradicate a tumor completely. There are certain mechanisms by which chemotherapy inhibits cancer. The first mechanism is cell death by cytotoxicity. Some chemical agents in certain amounts are toxic to cells. The cells die due to the toxic...
Why do consumers purchase specific drugs for various ailments, sicknesses or diseases they might have? Why do physicians prescribe certain drugs over competitive drugs that may be available to the public? Why is it that most of us can easily name specific drugs that fit the many ailments of today’s society? On the surface the answer might be as simple as good TV advertising or radio commercials or even internet adds. The truth of matter is the major pharmaceutical manufacturers own the patents on these drugs and this gives them all of the marketing budget and muscle they need to promote the drug and control the pricing. The incentives for larger pharmaceutical companies are very enticing and as a result, they don’t mind spending the time in clinical trials and patent courts to get their drugs approved. Some will even get patents on the process by which the drug is manufactured, ensuring that no competitor can steal the drug or the process. This protects their large financial investment and nearly guarantees a large return for their investors. Many consumer rights groups claim this is nothing more than legalizing monopolies for the biggest manufacturers.
was designed to avoid mislabeled food and drug products and was the start of making sure every
Cancer in one way or another touches all of us, whether as a patient or through the diagnosis of the people you love around you. Millions of patients who are faced with cancer are depending on oncologists everywhere to cure cancer so others will not suffer like they had to. Optimistically, sooner rather than later this international problem will come to an end. There are a number of drug companies that have been coming out with cancer treatment drugs. “Oncology has been one of the hottest and most active therapeutic areas for drug development, drug makers may want to take note of a finding that new cancer drugs have proven far more difficult to gain approval than medicines for infectious and autoimmune diseases.” (nature.com) Unfortunately, these drugs cannot cure the cancer but it sure makes it a load easier o...
Photodynamic therapy (PDT) has proven to be an encouraging therapy used in treating metastatic melanoma skin cancers. There are three requirements for PDT to be successful: a photosensitizer (PS), light, and oxygen in the tumor site. One problem with current PS is their inability to penetrate deeply. A suggested PS is chlorin e6 (Ce6) because of its high singlet oxygen quantum yield, bright fluorescence, and rapid clearance from the body. However, there are some challenges with Ce6 as it is not water soluable, has poor pharmacokinetics, and lack of the ability to specifically target the tumor. To help solve these challenges, Ce6 was conjugated to carbon dot (Cdot). This helps Ce6 be more water soluble and extend the half life in the blood. Additionally, Cdot indirectly excites Ce6 by Forster fluorescence resonance energy transfer. Cdot is also nno-cytotoxic, and has a cheap
Almost everyone is touched by cancer in some way and the number of people living with and beyond cancer grows greater every year. Globally 14 million people are diagnosed with cancer each year and 8 million people will die from it annually. Half of all men and one-third of all women will develop cancer during their lifetime. (13) There are many treatments for cancer, mainly: surgery, radiation and chemotherapy. These traditional treatments have many negative side effects. Therefore, increasingly, other treatments, such as hormonal therapy and targeted therapy are being used for certain cancers. Nanotechnology is a form of targeted therapy that destroys cancer tumors with minimal damage to healthy tissues and organs. Scientists are already using nanotechnology in early detection of elimination of cancer cells before they form tumors. But the real game changer will be when nanotechnology targets cancer tumors in treatment (11,13).
Cancer is one of the leading causes of death worldwide as it can develop in almost any organ or tissue. Significant advances in understanding the cellular basis of cancer and the underlying biological mechanisms of tumour has been vastly improved in the recent years (Jiang et al. 1994). Cancer is a genetic disease which requires series of mutation during cell division to develop, it has characteristics which can be associated with their ability to grow and divide abnormal cells uncontrollable while in the mean time invade and cause nearby blood vessels to serve its need. Even though many people are affected by cancer today, the abilities which cancer cells own make it hard to find single effective treatment for cancer. The focus of research now lies on developing drugs which target cancer cells in the hope to cure cancer once and for all.
The most common type of radiation therapy that is used involves exposure of patients to external radiations. In this method, a beam containing high-energy X-rays is directed to a specific region of the body to irradiate the main tumors. However, the problem with this technique is that the ability to hit normal tissues of adjacent organs (Noda et al., 2009). Different from this, targeted radionuclide therapy functions like chemotherapy. A radionuclide labeled molecule is administered either orally or intravenously such that it delivers radiations that are sufficiently toxic to the site of the disease to kill the target cells (Bolus & Brady, 2011). However, the main difference with chemotherapy is that the drugs or toxins only...
The American Cancer Society publishes current advances made in cancer research on their website. Many of the exciting discoveries about how best to treat the disease focus on the genetic aspects associated with certain types of cancer. In addition, treatments aimed at genetic solutions to cancer may be more effective and may cause fewer adverse side effects than traditional cancer treatments (American Can...
Bioengineering analysis is pointing a new way to better drug designs and better drug testing. The disease of cancer has taken the life of many patients, but through new medicines and procedures many more are surviving. A significant progress has been made against cancer, allowing people to live longer and fuller lives. There have been more than one-million less cancer deaths since 1990and 1991(aacr.org). On January 1, 2012 there were 13.7 million survivors in the United States. These numbers are achieved by using new techniques to cure cancer like, immunotherapies to avoid toxins, Targeted cancer therapies to target different types of cancer, and weakling cancerous tumors making them susceptible to drugs. Cancer is still a significant problem and is far from being cured, but step by step biomedical engineers are getting closer and closer.