Skip to 0 minutes and 15 secondsIn this video, we're going to consider current treatments used in the management of cancer. I'll outline the types of treatments that we use, the aims of these treatments. And we'll describe their successes and also limitations. The treatment of a cancer will often involve several different types, or modalities, of therapy. It's helpful to consider these therapies as belonging to one of two categories. First, there are local therapies. These are treatments that are focused on a specific area within the body. Often, this will be the primary tumour. And they do not affect areas beyond this. Local therapies include surgery and radiotherapy. Surgery, in particular, is often the most effective way of removing a primary cancer with the aim of cure.
Skip to 1 minute and 6 secondsRadiotherapy consists of high-energy radiation, usually x-rays, generated by a linear accelerator, such as the one shown here. And these x-rays can be directed very accurately to a localised area within the body. These high-energy x-rays can then destroy cancer cells in the treated area by damaging their DNA. But we'll look at radiotherapy in more detail in another video. The second category is systemic therapy. This includes chemotherapy, endocrine therapy, and biological or targeted therapies. By systemic, we mean treatments that are applied to the whole individual rather than just to a single site. So typically, these are treatments that are administered orally or by injection, enter the circulation, and are then distributed throughout the body.
Skip to 1 minute and 59 secondsSo systemic therapies can treat cancer at multiple sites throughout body. However, even systemic therapies can have difficulty in reaching every organ and tissue. For example, it can be difficult for many systemic therapies to enter the brain and central nervous system. Now, let's look at each of these in turn. There are many classes of cytotoxic drugs. Some are shown on this slide. What these drugs have in common is that they all work by interfering with processes of cell replication by preventing DNA synthesis or by damaging DNA or by blocking cell division. This means that they target rapidly dividing cells. Cancer cells tend to be more sensitive to these drugs than normal cells but often the difference in sensitivity is relatively small.
Skip to 2 minutes and 50 secondsSo typically, these drugs will also target other rapidly dividing cells. For example, precursors of white blood cells in the bone marrow, cells in the hair follicle, and the epithelial lining of the gut. This means that many of these drugs are associated with side effects, such as hair loss, a weakened immune system with the risk of infection, and gastrointestinal symptoms, like diarrhoea. Some cancers depend on hormones for their growth and survival. In particular, this includes estrogen-receptor-positive breast cancer and also prostate cancers that require androgens. This means that we can manipulate the hormonal environment within a patient to target these cancers. We can do this by using drugs such as LHRH analogues.
Skip to 3 minutes and 42 secondsIn pre-menopausal women, this type of drug will stop the ovaries producing oestrogen and, in men, will stop the testicular production of androgens. After the menopause, ovaries no longer produce oestrogen. But circulating androgens, produced in the adrenal gland, are converted to oestrogen by an enzyme called aromatase. And so a class of drugs called aromatase inhibitors can be used to reduce oestrogen levels in postmenopausal women. So all of these drugs work by reducing the levels of oestrogen or androgen in the body and, so, depriving the cancer of the hormone that it requires. Another way of targeting endocrine responsive cancers is with drugs that block the hormone receptor within the cancer cell itself. And this is how drugs like Tamoxifen work.
Skip to 4 minutes and 35 secondsMost of the recently developed drugs are known as targeted or biological therapies. These drugs exploit our increasing knowledge of the mechanisms underlying the hallmarks of cancer. These drugs are designed in a very specific way to target a particular protein that may be important in a particular type of cancer. Often, these drugs are developed to target the protein produced by an oncogene and to specifically block its function. An example would be the drugs Trastuzumab and Lapatinib both of which target the HER2 protein that drives an aggressive sub type of breast cancer. These drugs tend to have very different side effects to those of cytotoxic chemotherapy drugs. And hair loss and immune suppression are uncommon with most targeted therapies.
Skip to 5 minutes and 28 secondsHowever, they can have a range of other side effects, often related to their mechanism of action. For example, HER2 targeted drugs can occasionally cause problems with cardiac function because HER2 is also expressed in normal heart cells and is important for their function.
Skip to 5 minutes and 48 secondsOther targeted therapies have been designed to influence the host or patient rather than the cancer cell directly. An example would be drugs that prevent angiogenesis or drugs that can stimulate the body's immune response to a cancer. So now we have considered a range of local and systemic therapies. But how do they fit together in the overall management of cancer? To explore this, let's take a hypothetical patient, a woman with a newly diagnosed breast cancer. This woman has presented with a lump in her breast and has no signs or symptoms to suggest that the cancer has spread any further.
Skip to 6 minutes and 28 secondsSo the best treatment here is surgical removal of the primary breast cancer followed by radiotherapy to deal with any tiny areas of cancer that may have been left behind in the breast. This local treatment will be sufficient to cure many patients. Other patients, unfortunately, will eventually relapse months or years later with metastatic disease in distant organs, such as bone, lung, or liver. When this happens, metastases are usually disseminated, or spread, throughout the body and so cannot be removed using local treatments, like radiotherapy, or surgery, although these may be useful to treat individual sites of metastases that are causing particular problems like pain or bleeding. However, to tackle cancer throughout the body, we would use systemic therapies.
Skip to 7 minutes and 25 secondsThe particular systemic therapy, or combination of therapies, depending on the type of cancer being treated. This can let us shrink down or prevent further growth of metastatic cancer. But at present, our treatments are not good enough to eliminate metastases and cure our patient. What this means is that when we use systemic therapies to treat metastatic cancer, we do so with palliative, rather than curative, intent. In other words, to extend life, to palliate symptoms, and to maintain quality of life. This is the case for metastatic breast cancer and for most of the common cancers. But there are some exceptions.
Skip to 8 minutes and 11 secondsFor example testicular cancer is very sensitive to chemotherapy and so can usually be cured even when it has spread to distant organs. But can we interrupt this progression from potentially curable primary cancer to incurable metastatic cancer? Metastases can develop when microscopic clusters of cells have already managed to leave the primary site before diagnosis and surgery. These clusters of cells are not detectable on standard imaging or blood tests and are often called micrometastases.
Skip to 8 minutes and 53 secondsAlthough our systemic therapies are not able to eliminate metastatic disease, it turns out that often these same therapies can successfully eliminate the much smaller micrometastases if they're given just after surgery to the primary tumour. We call this adjuvant treatment. By using systemic therapies this way, many patients who would have developed fatal metastatic disease have instead been cured. And this has been one of the biggest successes in cancer therapy over the past 30 years.
Current clinical management of cancer
Dr Iain MacPherson describes the current clinical management of cancer.
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