Cancer research in the 21st Century

Studies that attempt to determine the underlying causes of cancer, including molecular changes in the cell, and work toward improved methods to cure or control the disease

Twenty-first century research into the causes of cancer resulted in improved understanding of the genetic and molecular changes that take place during the transformation of normal cells into malignant ones. Applications of this knowledge resulted in further development of therapies that focus on characteristics specific to the cancer.

Beginning in the 1970s, the identification of genes that regulate cell division began the process of understanding the molecular biology of cancer. Because aberrant regulation by these genes may result in cancer formation, they became known as oncogenes. By the 2000s, over one hundred such genes had been identified. Many function as either cell surface receptors, stimulating cell division, or as intermediates in pathways that activate genetic elements of DNA, regulating cell division. Because some of these pathways are unique to certain cancer cells, they have become targets of new generations of anticancer drugs, reducing the dangerous side effects often associated with chemotherapy.

Targeting Specific Cancers

Imatinib, the first of the anticancer drugs to specifically target a form of leukemia, was approved by the Food and Drug Administration (FDA) in 2001 to combat chronic myelogenous leukemia (CML). CML is characterized by the “Philadelphia chromosome,” a translocation of an oncogene from chromosome 9 to chromosome 22. The result is uncontrolled regulation of an enzyme known as tyrosine kinase, which functions in the regulation of cell growth. Imatinib specifically inhibits the enzyme, preventing replication of CML cells. Imatinib was subsequently found to target a second form of cancer, gastrointestinal stroma tumor.

In 2003, the FDA approved two drugs targeting certain forms of lung cancer: gefitinib and erlotinib, each of which inhibits a cell surface protein (a growth factor receptor) on lung cancer cells. While results with gefitinib have been mixed—it remains unclear whether its use extends life expectancy—erlotinib use has been extended to treat pancreatic cancers.

Since tumor growth requires a blood supply, cancer cells produce angiogenic agents, molecules that stimulate the formation of blood vessels. In 2004, the FDA approved the first drug that targets angiogenesis, bevacizumab, which blocks blood vessel formation. The drug has proven useful in treating a variety of cancers, including those of the colon or rectum, lungs, ovaries, and brain. Additional drugs targeting colorectal cancer were also approved in the 2000s, such as panitumumad (2006). In a manner similar to that of erlotinib, these drugs target the growth factor receptor on the surface of cancer cells.

Earlier Detection of Cancer

In the 2000s, lung cancer superseded breast cancer as the most common cause of cancer deaths in women, and has remained the highest cause of cancer mortality in men, with nearly 160,000 persons dying from the disease each year. Since smoking is the primary cause of most lung cancers in both men and women, improved screening methods have been used for earlier diagnosis. In 2010, a trial funded by the National Cancer Institute determined that low-dose spiral CT scans (LDCT) of persons at greatest risk for lung cancer reduced cancer mortality by 20 percent over the course of the study. Longer-term observations will be necessary to determine whether earlier diagnosis translates into a longer life expectancy.

Since surgery remains the primary means of treating lung cancer, several methods were introduced during the decade to make surgery less invasive. Often lobectomy, the removal of an entire lobe—in this case of the lung—is the method of choice to better ensure that the cancer has been removed. Studies began comparing the efficacy of lobectomy with the less radical surgery of removing only the tumor and some of the surrounding tissue. Other surgical procedures attempt to avoid the necessity of opening the entire chest. The technique of video-assisted thoracoscopic surgery (VATS), which allows the surgeon to enter the chest through a significantly narrower opening, also began to be tested during the 2000s. Prevention of lung cancer remains the primary goal. Since smoking is the most important environmental factor and can be controlled, education on the dangers of smoking was increasingly emphasized.

Prostate cancer remained the second leading cause of cancer deaths among men, with the American Cancer Society estimating that over 25,000 men will die each year from the disease. Early detection has historically relied on a test that measures prostate specific antigen (PSA), a protein found in association with prostate cells. The PSA test has proven controversial, often missing some forms of prostate cancer while producing frequent false positive results, leading to unnecessary biopsies. The efficacy of yearly PSA testing for most men remains uncertain. A test called PCA3, developed in the 2000s and approved by the FDA in 2012, screens for the presence of a mutation common in most forms of prostate cancer. Though more difficult to run in the laboratory, the increased accuracy of the PCA3 test may result in its replacing that of the PSA screening.

Cancer Vaccines

The National Cancer Institute has defined two categories of anticancer vaccines: (1) those that prevent cancer through immunization of persons against the etiological (causative) agent of the disease, and (2) vaccines that can treat cancers that have already developed, harnessing the immune system in the attack. The hepatitis B vaccines introduced in the 1980s, while indirectly protecting against development of hepatocarcinoma (a type of liver cancer), were targeting hepatitis B virus infections in general. The first vaccine that focused specifically on a type of cancer was Gardasil, approved by the FDA in 2006 to immunize women against cervical cancer. The vaccine contains protein subunits from the four most common types of human papilloma virus (HPV 6, 11, 16, and 18), the etiological agent of the disease. A similar vaccine, Cervarix, directed against HPV 16 and 18, was approved by the FDA in 2009. While initial studies focused on immunizing women against HPV, the recognition that the same virus may cause anal, penile, and oropharyngeal cancer in men has resulted in recommendations that men also receive HPV immunization.

In 2010, the FDA approved the first vaccine for treatment of an existing cancer, that of the prostate. The development of Sipuleucel-T is an example of the application of new techniques in molecular medicine. The vaccine is directed against a specific protein—prostatic acid phosphatase (PAP)—an enzyme located on the surface of prostate cancer cells. The procedure involves the isolation of a subset of immune cells, antigen-presenting cells (APCs), from the patient and incubating them with purified PAP. Once the APCs have been stimulated, they are reinfused into the patient, resulting in a significant increase in the immune response against the cancer.

Impact

Gardasil and Cervarix have proven effective in preventing precancerous lesions associated with HPV infection; few significant side effects have been reported. Field trials that included placebos were so definitive that testing was terminated, with recipients of the placebo allowed to receive the actual vaccines. Long-term studies remain necessary to determine the precise impact on the yearly incidence of cervical cancer. Politics has, however, played a role in the decision as to whether the HPV vaccine should be required for women prior to puberty; some conservative groups have argued that doing so would send a message encouraging premarital intercourse.

The long-term efficacy of targeted treatments of cancer remains to be determined. Nevertheless, through the first decade of the twenty-first century, some 12 million people became cancer survivors, a number up by 20 percent since the beginning of the decade.

Bibliography

Hesketh, Robin. Introduction to Cancer Biology. New York: Cambridge UP, 2012. Print. The story of cancer for the nonscientist, included the role played by molecular pathways in the cell that normally regulate cell growth.

Mukherjee, Siddhartha. The Emperor of All Maladies: A Biography of Cancer. New York: Scribner, 2011. Print. Covers the disease’s first recognition in ancient Egypt through modern understanding and treatment.

Olson, James. Bathsheba’s Breast: Women, Cancer, and History. Baltimore: Johns Hopkins, 2002. Print. The title originates from the observation that the image of Bathsheba in Rembrandt’s painting Bathsheba at her Bath shows evidence of breast cancer. Rembrandt’s model had in fact died from that disease. The author, who also suffered from cancer, describes how a number of prominent women dealt with their own diagnosis of the disease.

Skloot, Rebecca. The Immortal Life of Henrietta Lacks. New York: Crown, 2010. Print. Story of the woman behind HeLa cells, which were used for decades in cellular research. Henrietta Lacks was an African American woman who died from cervical cancer in the early 1950s; samples of her cancer were removed and by chance proved relatively easy to grow in the laboratory. The author addresses both the biology of HeLa cells and the ethical dilemma involved.

Stockwell, Brent. The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines. New York: Columbia UP, 2011. Print. The history of chemotherapy as a treatment for diseases like cancer. Describes the challenges involved in the development of new generations of drugs as well as the future of personalized therapy.