Early Detection Tests And Potential Impact On Cancer Drug Development

By Merrilyn Datta, PhD, CCO and general manager, Definiens

In recent months, we’ve seen a rising focus on early detection methods for cancer. Data just surfaced on a urine test that may be able to detect pancreatic cancer at an early stage by looking at elevated levels of proteins LYVE1, REG1A, and TFF1, and non-invasive genomic tests are being developed to detect oral cancer in early stages right at the dentist’s office. Blood tests currently show great promise in early detection. University College London recently reported trial results on a test that is able to detect early stage ovarian cancer by tracking changing levels of a protein, CA125, in the blood. Tufts Medical Center found pre-natal blood tests could detect cancer in expectant mothers.

Advancements in early detection research raise questions as to whether breakthroughs, such as the CA125 blood test, will affect the future of drug discovery and development. Will the ability to detect cancers earlier shift the focus to treatments that are effective in earlier stages? What kinds of opportunities exist for the industry, and perhaps more importantly, what potential challenges might this trend bring to pharmaceutical development?

Focus On Early Detection

Early detection of cancer is becoming increasingly important due to the immense value it can provide to patients and the overall health system. Looking at ovarian cancer as an example, around 21,000 new cases are reported per year in the U.S., yet only 15 percent of them are diagnosed as early stage. Yet, studies show that the 5-year survival rate for patients diagnosed early is over 90 percent, and the survival rate drops to as low as 22 percent for those diagnosed in late stages. Similar statistics exist for breast cancer, pancreatic cancer, and melanoma. Clearly, early detection methods could make a huge difference for these disease states.

While some cancers already can be detected in early stages, early detection rates are unfortunately still low. This could be because regular physicals and annual mammograms, skin checks, and other check-ups are not a priority for the average American due to the time and effort they require. Advancements with less invasive diagnostics, such as a simple blood test, are thus important as they represent a lower barrier to entry; with easier testing, we may see a greater percentage of earlier detection and a lower percentage of patients who present with late stage cancer.

Given these factors, the industry is in a race to develop the simplest, least invasive cancer screenings. In particular, there is significant buzz around leveraging circulating tumor cells (CTCs) in the bloodstream as diagnostic targets. CTCs are released from primary tumors into blood circulation and spread to other areas of the body, creating new cancer growth, and are a major factor in patient mortality. The detection of CTCs is thus seen by many as the future of early detection and even cancer prognosis. While important to early detection, blood tests alone won’t necessarily impact the drug development or patient treatment process – more information is needed.

From Blood Tests To Biopsies

Early detection is incredibly important and could have a huge impact on the percentage of people with positive 5-year survival rates, but it is only the initial step. In order to diagnose and understand the cancer, solid tumor imaging and tissue data analysis is required. Thus, as more early detection methods come to fruition, an increased focus must also be placed on solid tumor analysis. In particular, analysis of the immune response in the tumor microenvironment is creating great excitement around successful cancer therapies.

Early detection methods should be viewed as an important complementary technology to evolving genomics and tissue data analysis technologies. All three are necessary to the advancement of drug discovery and development and ultimately patient treatment, and must work together in concert. For example, in an ideal scenario, a blood screening would indicate the presence of cancer, a genetic test would derive a possible driver mutation, and tissue analysis on the tumor would provide information on how the cancer is behaving and how it should be treated. Solid tumor imaging provides key information about the disease for that patient’s treatment as well as the research and development of new therapies.

Impact On Drug Development

With more robust early detection methods on the horizon, drug developers are at a juncture where they need to consider what to develop or what recommendations to provide doctors, whether from a formulation, dosing, or drug development perspective, to best treat patients who are diagnosed with earlier stage cancers.

Many drug trials and therapies currently focus on patients with late stage cancers for a variety of reasons. It is less challenging to garner approval on later stage drugs vs. early stage drugs, in part because the clinical trial system is structured in a way that recruits patients with very few alternatives. The advancement of early detection thus raises a few important considerations for the drug development industry:

• Are there molecules or drugs that may work better for early rather than late stage patients?
• If so, how do we recruit those patients who are early stage and not necessarily looking for alternative options yet into clinical trials, which they may perceive as risky?

Clinical trial design may also need to be revisited. For example, if current clinical trial design is set up to look for significant tumor shrinkage, as is often the case, the trial may be more difficult to apply to early stage cancer research. Trial design may need to include stratifying patients differently to study early and late stage cancers separately.

Finally, drug development based on early detection is only the first part of the equation. The second piece is education or regulatory guidelines to incite an action on the part of patients or physicians when cancer is detected early. If a pharmaceutical company develops a treatment for early stage cancer, ultimately physicians need to have knowledge of it and guidelines for what to prescribe or how to treat patients that test positive in early stages.

These are the questions the industry will need to start considering as it looks toward developing personalized therapies to treat patients diagnosed earlier than previously possible.

Opportunities For Drug Developers

Early detection is extremely important, and there are many unique technologies being developed in this field – but there are also hurdles. In the case of blood tests, circulating tumor cells in the blood may be one in millions – the parabolic needle in a haystack – so any blood test developed needs to have outstanding detection ability. More research and advancements are needed to truly realize the potential of cancer screening tests. This is where the industry is moving, however, and while there are challenges, there are opportunities as well.

In general, early detection, of course, has the most benefits for patients, as well as the overall healthcare system since, if more patients are brought into remission easier, fewer costs are garnered. However, early detection also represents a big opportunity for drug developers. On the one hand, early detection may encourage more people to take advantage of preventative care options, which has implications for other kinds of drugs pharmaceutical companies could develop. Additionally, early detection could mean working with a wider population, using drugs they already have on the market as well as developing new ones based on the early detection tests.

One area that has cancer researchers extremely excited is immuno-oncology. Many experts believe immuno-oncology is the future of cancer care since it has shown significant promise in pulling patients into remission for extended periods of time. Most of the assays being developed currently are studying immune cells and how they invade tumors, and an investment in treatments that stimulate the immune system could have a significant impact on early cancers. This should be a key area of focus for drug companies.

As the industry increasingly moves toward early detection, drug companies have an opportunity to evaluate the landscape and adjust their strategies as needed in preparation for an era where more people will present with early stage cancer rather than be handed a late stage diagnosis.

About the Author

Merrilyn Datta is Chief Commercial Officer and General Manager of Definiens, the Tissue Phenomics company, and has more than 15 years of commercialization experience within the life sciences and diagnostics industry. Dr. Datta joined Definiens from Life Technologies where she held a variety of roles in leadership, strategy of technology commercialization, and mergers/acquisitions.