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Nanoparticles in Cancer Treatment
I have been asked by multiple patients recently about nanoparticles for use in the treatment of cancer. Nanoparticle research has generated considerable coverage in the lay press over the past year and a half, including a CBS 60 Minutes episode titled “The Kanzius Machine: A Cancer Cure?”.
The term “nanoparticles” refers to very tiny particles, much smaller than cancer cells or even standard chemotherapy drugs. A nanoparticle ranges between 1 and 100 nanometers (a metric unit of length equal to one billionth of a meter) in diameter. Nanoparticles have industrial uses in creating surface coatings for scratch-resistant glass, skid-resistant roads, in strengthening metals, and in the development of more efficient solar panels. This post will concentrate on the applications related to cancer therapy.
There are basically two main areas in which nanoparticles are being explored in relation to cancer: molecular imaging and therapy. In molecular imaging, nanoparticles are injected into the body and taken up by cancer cells, with the uptake causing the cancer cells to show up differently than normal surrounding cells (from Google images).
Nanoparticle
Update on Denosumab for Prevention of SREs
Back in April I reviewed the use of Aredia, Zometa, and denosumab for the prevention of skeletal-related events (SREs), in patients with cancer with bony metastases. SREs, defined as pain or fracture in a bone from cancer involvement, can result in the need for radiation, surgery, or other intervention, and consequently is damaging to the quality of life of patients with advanced cancer.
At that time, denosumab had been studied primarily in the treatment of osteoporosis, although a number of trials were ongoing in cancer patients. The only published large randomized trial in cancer patients at that time compared denosumab to placebo in women with surgically-resected breast cancer who were receiving endocrine therapy. Denosumab or placebo was administered every 6 months, with the outcomes of measuring an increase in bone density. Denosumab was shown to be better than placebo at increasing bone density. Measurement of SREs was not the goal of this trial.
An Emerging Potential Therapy for Bone Health: Denosumab
In my last post, we covered an introduction to bone metastases and the use of the class of drugs known as bisphosphonates as a current standard treatment. A new investigational approach is also being tested, known as denosumab (AMG-162), which is a different from the bisphosphonates. A monoclonal antibody, denosumab is designed to attach to and inhibit an activating factor in the blood (termed a ligand) that stimulates the function of osteoclasts (the cells breaking down bone), thus providing a novel way of decreasing bone resorption. The ligand in this instance is called RANKL (which stands for Receptor Activator of Nuclear Factor-KappaBeta Ligand).
(Click to enlarge)
The early research in this field was in the treatment of osteoporosis. Denosumab is given as a subcutaneous injection (under the skin), and different studies have used different time intervals between injections: 1 month, 3 months, or 6 months.
Overview of Bone Metastases and Bisphosphonate Treatment
A query was recently raised about the use of denosumab for the treatment of bony metastases from lung cancer. We’ll cover what is known about that newer agent for bone metastases, but first let’s set the stage with a general discussion of the topic and the management options we’ve generally pursued over the past few years.
To put things into context, when a cancer spreads to bones, the chief concerns are that the tumors can cause pain, as well as a risk of fracture in those bones. Depending on the location of the bones involved, fractures can have consequences beyond just the pain. For example, a break in a hip bone may require surgery in order to help a patient maintain the ability to walk, etc.
With lung cancer, for large bone metastases that are already symptomatic or at risk of breaking, generally the first treatment of choice is radiation to that area. This can help to relieve pain, and to strengthen the bone and decrease the risk of the bone breaking. If a bone in a weight-bearing area (the upper arms and legs in particular) has broken or is at too high of a risk for breaking, surgery may be required to stabilize that region.
Chemotherapy can also help to decrease the symptoms from bone metastases by treating the cancer cells directly, while at the same time treating cancer cells wherever else they may be located in the body.
Questions have been raised however about what to do with cancers that have spread to many different bone locations, or who have small bone metastases that do not require radiation. These patients may be at risk for pain or fracture in the future, but not necessarily immediately. Is there anything that can be done to decrease that risk of developing pain? Can the risk of fracture (which by the nature of a risk, may or may not happen), be reduced or delayed?
Such an event (pain or bone fracture) in the medical literature is termed a skeletal-related event, or SRE for short.
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