Until the late 1990s nearly all drugs used in cancer treatment (with the exception of hormone treatments) worked by killing cells that were in the process of replicating their DNA and dividing to form 2 new cells. These chemotherapy drugs also killed some normal cells but had a greater effect on cancer cells. Targeted therapies work by influencing the processes that control growth, division, and spread of cancer cells, as well as the signals that cause cancer cells to die naturally (the way normal cells do when they are damaged or old). Targeted therapies work in several ways.
a. Antisense oligodeoxynucleotides and small interfering RNA (siRNA). An example of this is a new class of targeted therapies called PARP inhibitors. (PARP is short for poly (ADP-ribose) polymerase enzymes.) Cancer cells use PARP to repair DNA damage, including the damage caused by cancer treatment. Recent studies in breast cancer have shown that blocking PARP can make cancer cells more sensitive to treatment and promote cell death. BRAF is another gene that can produce a mutant cancer protein seen in about half of all melanomas. The drug vemurafenib (Zelboraf) targets this mutation. This drug prolonged overall survival in patients with inoperable melanoma compared to the standard drug dacarbazine. Vemurafenib was FDA approved in August 2011 for patients who have melanoma with this gene mutation.
b. Growth signal inhibitors During the 1980s, scientists found that many of the growth factors and other substances responsible for recognizing and responding to growth factor are actually products of oncogenes. Among the earliest targeted therapies that block growth signals are trastuzumab (Herceptin), gefitinib (Iressa), imatinib (Gleevec), and cetuximab (Erbitux). Current research has shown great promise for these treatments in some of the more deadly and hard-to-treat forms of cancer, such as non-small cell lung cancer, advanced kidney cancer, and glioblastoma. And second-generation targeted therapies, like dasatinib (Sprycel) and nilotinib (Tasigna), have already been found to produce faster and stronger responses in certain types of cancer and were better tolerated.
c. Angiogenesis inhibitors. Anti-angiogenesis agents are types of targeted therapy that use drugs or other substances to stop tumours from making the new blood vessels they need to keep growing. This concept was first proposed by Judah Folkman in the early 1970s, but it wasn’t until 2004 that the first angiogenesis inhibitor, bevacizumab (Avastin), was approved. Currently used to treat advanced colorectal, kidney, and lung cancers, bevacizumab is being studied as treatment for many other types of cancer, too. And many new drugs that block angiogenesis have become available since 2004.
d. Apoptosis-inducing drugs Apoptosis is a natural process through which cells with DNA too damaged to repair – such as cancer cells – can be forced to die. Many anti-cancer treatments (including radiation and chemo) cause cell changes that eventually lead to apoptosis. But targeted drugs in this group are different, because they are aimed specifically at the cell substances that control cell survival and death.
e. Nanotechnology: New technology for producing materials that form extremely tiny particles is leading to very promising imaging tests that can more accurately show the location of tumours. It also is aiding the development of new ways to deliver drugs more specifically and effectively tocancer cells