When I was diagnosed with a potential precursor to breast cancer, ductal carcinoma in situ, three-and-a-half years ago, very few things were reassuring, especially for a cancer researcher like myself with a clear understanding of the potential consequences of my diagnosis. One thing did provide me with some comfort: that my tumor had an alteration in the HER2 gene, which meant that, if I needed treatment, there was a chance it would be susceptible to several drugs, called “targeted therapies,” that interfered with tumor cells with high levels of HER2.
The advent of “targeted therapies” has transformed the treatment of several types of cancer and is impacting the design of clinical trials. The result is the development of strategies to fight cancers in ways that are providing tremendous benefit for patients. A breakthrough in cancer treatment –finding treatment regimens that extend the life of patients with advanced cancer for unprecedented lengths of time – is on the horizon. However, cuts to funds for biomedical research threaten to jeopardize this progress right when we stand to benefit the most. Since one in four people in the United States die of cancer, we cannot afford to hinder this extraordinary progress.
Many cancers have specific alterations in proteins that are essential for the survival of the cancer cells. Targeted therapies are a class of anti-cancer agents that take advantage of this vulnerability, and prevent these altered proteins from working effectively. This causes cancer cells, most frequently, to either die or stop dividing. So, breast cancers with HER2 alterations may shrink upon treatment with a drug that blocks HER2. Likewise, drugs that target alterations found in subsets of lung cancers, leukemias and melanoma are FDA-approved for use in these patients.
The success of targeted therapies has created a paradigm shift in how we think of treating cancer. Prior to these discoveries, many cancers of a given type were treated in the same way, usually with chemotherapy. Now, in many centers, some cancers undergo molecular testing and the patient is treated according to the molecular features present in the tumor, an approach described as “precision-medicine.”
Immunotherapies are another up-and-coming class of targeted therapies that are designed to boost the ability of the immune system to fight cancer cells. These drugs are showing great promise in several cancers and are undergoing very rapid clinical development.
During breast cancer awareness month, it is useful to reflect on the origin of these successful cancer therapies, and think about how we can ensure continuous progress in the quest for curative cancer treatments. One thing is clear: we wouldn’t have any of those successful therapies without an enormous government investment in research, and our progress toward cures won’t be sustained without ongoing investment, either.
The development of trastuzumab, an antibody that targets HER2, was the culmination of approximately fifteen years of intense laboratory work and rigorous clinical trials that led to its approval by the FDA in 1998. Since then, the number of targeted therapies and the speed with which they reach the clinic has increased. This year, all of the new oncology drugs approved to date are a targeted or immuno-therapy. Once such drug, ceritinib, was recently awarded breakthrough status for the treatment of certain lung cancers that have alterations in the ALK gene. Underscoring the possible speed with which basic discoveries can be translated to the clinic, alterations in ALK in lung cancer were first discovered in 2007 and the first targeted therapy, crizotinib, received accelerated FDA approval to treat this disease in 2011.
But are targeted therapies better than standard treatment regimens? Several examples indicate that this is the case. In breast cancer, it is now well-established that the addition of trastuzumab to chemotherapy reduces the relapse rate for women with early-stage HER2 positive breast cancer. And, in those patients with metastatic disease, use of drugs targeting HER2 extends survival compared to chemotherapy alone. In data presented last week at the European Society of Medical Oncology, using a treatment strategy that combined two drugs targeting HER2 compared to one that included only one of the HER2 drugs, increased the survival of patients with metastatic HER2 positive breast cancer by almost 16 months, a very significant improvement for patients with this disease. Similar patterns are emerging in subsets of lung cancer, like those with ALK alterations, in which the targeted therapy crizotinib has been shown to slow down disease progression better than chemotherapy. This progress is the direct result of research that has provided insight into how cancer cells function, studies of the genetics of cancer cells and clinical trials directed towards relevant subsets of patients.
Despite their promise and benefits, targeted therapies are not perfect, and they certainly aren’t magic. For example, they fall short when it comes to achieving cures in patients with metastatic cancer. Resistance to these drugs almost inevitably develops and is a major challenge faced by clinicians, scientists and patients alike. Moreover, targeted therapies have only been identified for specific subsets of cancer, and much research still remains to be done to identify new targets and new drugs so that we can increase the number of patients who can benefit from this approach. Finally, with regard to immunotherapies, we are only beginning to understand when and how to use this promising class of drugs. To tackle these problems, the biomedical research community requires sustained, dependable funding that can provide us with the focus necessary to devote our attention to these critical issues.
However, the National Cancer Institute budget has remained flat for almost a decade, and in fact, it suffered a significant decrease in 2013 because of sequestration. As a consequence, the success rate for grant applications has decreased by close to 50 percent since 2003 and scientists are reducing the size of their labs. Some are even choosing to perform experiments using approaches based on cost, rather than scientific value. Eventually, labs without funding have to close down. The risks of this contraction in the number of labs are incalculable, and we may not see the direct consequences of these funding decisions (e.g. a reduction in the number of novel therapeutic strategies to enter clinical trials, fewer groundbreaking discoveries about cancer cells and processes), for years to come. Still, the time to act is now. In the upcoming midterm elections, let’s elect candidates who will act on this problem, and in 2016 elect a President who is committed to improving our scientific enterprise.
Ten years ago, when people asked me why we hadn’t yet “cured” cancer, I would mumble a vague response about the complexity of the problem. Today, my answer is very different. There are many concrete examples of how investments in cancer biology are paying off and directly impacting patient care. Now is not the time to dim the lights – it’s the best part of the show.
Politi, Ph.D, is an assistant professor of Pathology and Medicine (in the section of Medical Oncology) at the Yale University School of Medicine, and an OpEd Project Public Voices fellow. She's a cancer biologist.