The first requirement is already partially met: we now have large catalogs of cancer-critical genes that are commonly mutated in cancer cells. The second requirement is harder, but attainable: we have described some remarkable recent successes, and for cancer researchers there is excitement in the air. It is becoming increasingly possible to use our growing knowledge of cell and molecular biology to design new drugs against designated targets. At the same time, efficient, high-throughput automated methods are available to screen large libraries of chemicals for any that may be effective against cells with a given cancer-related defect. In such searches, the goal is synthetic lethality: a cell death that occurs when and only when a particular drug is put together with a particular cancer cell abnormality. Through these and other approaches, the repertoire of precisely targeted anticancer drugs is rapidly increasing.
Figure 20–46 Why multidrug treatments can be more effective than sequential treatments for cancer therapy.
(A) Because tumor cells are hypermutable, two single-drug treatments that are given sequentially often allow for the selection of mutant cell clones that are resistant to both drugs. (B) Simultaneous treatment with both drugs can be more effective.
This brings us to the third requirement: the therapy—the choice of drugs to be given in combination—must be tailored to the individual patient. Here, too, the prospects are bright. Cancers evolve by a fundamentally random process, and each patient is different; but modern methods of genome analysis now let us characterize the cells from a tumor biopsy in exhaustive detail so as to discover which cancer-critical genes are affected in a particular case. Admittedly, this is not straightforward: the tumor cells in an individual patient are heterogeneous and do not all contain the same genetic lesions. With increased understandings of the pathways of cancer evolution, however, and with the experience gained from many different cases, it should become possible to make good guesses at the optimal therapies to use.
From the perspective of the patient, the pace of advance in cancer research can seem frustratingly slow. Each new drug has to be tested in the clinic, first for safety and then for efficacy, before it can be released for general use. And if the drug is to be used in combination with others, the combination therapy must then go through the same long process. Strict ethical rules constrain the conduct of trials, which means that they take time—typically several years. But slow and cautious steps, taken systematically in the right direction, can lead to great advances. There is still far to go, but the examples that we have discussed provide proof of principle and grounds for optimism.
From the cancer research effort, we have learned a great deal of what we know about the molecular biology of the normal cell. Now, more and more, we are discovering how to put that knowledge to use in the battle with cancer itself.
Our growing understanding of the cell biology of cancers has already begun to lead to better ways of preventing, diagnosing, and treating these diseases. Anticancer therapies can be designed to destroy cancer cells preferentially by exploiting the properties that distinguish cancer cells from normal cells, including the cancer cells’ dependence on oncogenic proteins and the defects they harbor in their DNA repair mechanisms. We now have good evidence that, by increasing our understanding of normal cell control mechanisms and exactly how they are subverted in specific cancers, we can eventually devise drugs to kill cancers precisely by attacking specific molecules critical for the growth and survival of the cancer cells. In addition, great progress has recently been made through sophisticated immunological approaches to cancer therapy. And, as we become better able to determine which genes are altered in the cells of any given tumor, we can begin to tailor treatments more accurately to each individual patient.
Which statements are true? Explain why or why not.
What is required to enable a cancer cell to metastasize?
how can the molecular analysis of an individual tumor be more effectively used to design effective therapies to kill it?
Can we identify general features common to all cancer cells—such as their production of misfolded, mutated proteins—that can be used for the targeted destruction of many different types of cancers?
Can sensitive and reliable blood tests be devised to detect cancers very early, before they have grown to a size where treatment with a single drug will generally be defeated by the survival of a preexisting resistant variant?