Guest post by Elizabeth M. Adler, PhD
Maryland Governor Larry Hogan, who was diagnosed several weeks ago with an aggressive form of B-cell non-Hodgkin lymphoma, has recently begun chemotherapy.
Lymphoma comes in an astonishing variety of “flavors,” making it difficult to comment on the governor’s prognosis without knowing his precise diagnosis. However, most B-cell lymphomas are highly treatable, and many people diagnosed with aggressive lymphomas have been cured. Lymphomas tend to be very responsive to chemotherapy, in which people are given antineoplastic (anticancer) drugs, usually injected into a vein or taken by mouth. Because most of the tissues in the body are exposed to these antineoplastic drugs, lymphoma chemotherapy can potentially cure even people with advanced stage disease that has spread to different areas of the body.
The basic idea underlying cancer chemotherapy is to destroy the malignant cells that make up the cancer, but spare the normal cells that make up healthy tissue. This approach to treating cancer depends on identifying chemotherapy drugs that can exploit the differences between malignant (cancer) cells and healthy cells. One of the most obvious differences between most cancer cells and most healthy cells is that cancer cells, oblivious to the molecular cues that restrain the growth and accumulation of healthy cells, can multiply like weeds taking over a garden. In an effort to take advantage of this difference, most classical chemotherapy regimens—and many chemo drugs used today—preferentially target rapidly dividing cells. Because these chemotherapy drugs act mainly against rapidly dividing cells, many of the aggressive forms of B-cell non-Hodgkin lymphoma (in which the malignant cells tend to divide rapidly) can be cured by chemotherapy regardless of the stage at which they are diagnosed. In contrast, advanced stages of the more slowly progressing forms of lymphoma, in which cancer cells tend to accumulate because of a failure to die at the appropriate time (rather than from too-rapid division), are not usually considered curable with current therapies.
In the early days of chemotherapy, the discovery of effective antineoplastic agents arose mainly from serendipitous (lucky) observations. For instance the discovery that mustard gas—used in chemical warfare during World War I—caused the destruction of lymphoid tissue and rapidly dividing cells in the bone marrow led to the development in the 1940s of the nitrogen mustards, a class of chemotherapy drugs still used to treat lymphoma and other cancers today. Similarly, researchers investigating the Madagascar periwinkle, based on its use in folk medicine to treat diabetes, discovered that, although plant extracts were ineffective against diabetes, they suppressed the bone marrow—an observation that led to the discovery of the antineoplastic vinca alkaloids (also still used to treat lymphoma and some other forms of cancer). More recently, researchers have taken a more directed approach to developing highly selective lymphoma therapies, such as using antibodies that specifically recognize proteins found only on the surface of B cells (and most B-cell lymphomas), enabling recruitment of the immune system into lymphoma therapy, and employing antineoplastic agents that specifically interfere with the intracellular signaling pathways that mediate B cell proliferation.
Just as populations of resistant bacteria can emerge following treatment with antibiotics, populations of cancer cells resistant to a particular drug can arise, so a cancer that initially responds to treatment with a particular drug can recur in a form that is no longer sensitive to that drug. Such resistance can occur because some of the cancer cells carry a mutation that allows them to survive exposure to the drug—and to give rise to a population of daughter cells that share their resistance. The observation that cancers can develop resistance to a form of single-agent therapy to which they were initially sensitive led to the development of combination chemotherapy, in which the cancer is treated with combinations of different antineoplastic drugs, each of which acts against cancer through a distinct mechanism. In the 1960s, Hodgkin lymphoma was among the first cancers successfully treated with combination chemotherapy. Curative chemotherapy regimens were developed for the non-Hodgkin lymphomas in the 1970s, but were not as effective as those used for treating Hodgkin lymphoma; the introduction of the monoclonal antibody rituximab in the 1990s was a true game-changer in B-cell lymphoma therapy, markedly increasing survival.
As someone diagnosed in 1996 with an aggressive B-cell lymphoma the size of a football, I was fortunate enough to stumble into the first clinical trial that combined rituximab with standard B-cell lymphoma chemotherapy. I’m happy to be alive—and cured of lymphoma—to wish Governor Hogan well, and to be able to say that he has good reason to be optimistic.
Elizabeth M. Adler, Ph.D., is the author of Living with Lymphoma: A Patient’s Guide. Trained as a neurobiologist, she shifted her focus to science communication and cancer advocacy following her diagnoses with lymphoma and breast cancer.