Building New Tools to Fight Stronger Foes: How Research is Making Inroads in the Early Detection and Treatment of Two Hard-to-Treat Cancers

1280px-Chronic_Lymphocytic_Leukemia

Chronic Lymphoblastic Leukaemia is a cancer of the blood cells, where white blood cells multiply too rapidly and crowd out other cells in the blood. Here, a blood sample from a leukaemia patient has been stained to differentiate between the classical donut-shaped red blood cells in light pink, and the much larger cancerous white blood cells in purple.

In this age of modern medicine, a cancer diagnosis no longer guarantees an untimely death. Many advances in cancer detection and treatment have been made over the past 30 years, and survival rates for the vast majority of cancers continue to improve. Unfortunately, not all cancer types benefit from a wide range of diagnosis and treatment options. For patients with a hard-to-treat cancer, there can be limited treatment options. When discussing hard-to-treat cancers, people typically think of brain, pancreatic, lung or esophageal cancers, however both ovarian cancer and Chronic Lymphocytic Leukemia (CLL) are cancers that come with unique challenges. Here I will discuss recent research and discoveries that are making inroads in both ovarian cancer and CLL.

Ovarian Cancer

Ovarian cancer is the fifth most common cancer among Canadian women but has the second-highest mortality rate, due in part to late diagnosis and challenges in treatment. Approximately 75% of patients are diagnosed when cancer has already spread to other parts of the body, and the 5-year survival for these late-diagnosis patients is just 20 – 40%.1,2 Unfortunately, almost half of all patients have their cancer return less than one year after treatment. For patients with recurrent cancer, there are limited treatment options.3,4 Recent research in the field of ovarian cancer is aiming to improve survival rates for this challenging cancer.

Early and accurate detection is key in halting ovarian cancer in its tracks – patients diagnosed with early stage disease (Stage I) have a 5-year survival rate of over 90%. One new way doctors are trying to improve the detection of ovarian cancer is by combining ultrasound imaging with biomarker analysis. Biomarkers, such as CA-125 for ovarian cancer, indicate the presence or severity of a particular disease. In the case of ovarian cancer, the biomarker CA-125 is a portion of a protein that is increased in patients with ovarian cancer. New computer programs can help doctors combine the information from ultrasound images with the results of the biomarker analysis to provide more accurate diagnoses, improving the time to treatment for many patients.5

While biomarkers are being tested to look at earlier detection of ovarian cancer, Circulating Tumour Cells (CTCs) in the blood of ovarian cancer patients are being studied for their ability to predict the aggressiveness of the disease or the course of treatment for patients. CTCs have been tested in clinical trials for a number of other cancers, ranging from breast to pancreatic cancer, and have been successful at predicting outcomes and overall survival6,7. The number of CTCs in the blood as well as their genetic make-up can help doctors determine the intensity and type of treatment required for a specific patient’s disease in a non-invasive fashion. Assays to measure CTCs have already been approved by the FDA, and are available in Canada. CTCs are currently being investigated as a means to identify both the spread and return of ovarian cancer sooner, so treatment can start earlier.

Chronic Lymphocytic Leukemia (CLL)

Another difficult cancer is Chronic Lymphocytic Leukemia (CLL), the most common blood cancer in the Western Hemisphere, which is largely considered to be incurable. CLL is typically diagnosed later in life. While almost 30% of patients have slow disease progression, which does not impact their life expectancy, 10% are diagnosed with an aggressive form of the disease and have a life expectancy of only 1-3 years. The remaining percentage of patients live with benign disease for 5-10 years, but it can be followed by rapid progression.8,9

One of the biggest breakthroughs in CLL research was the discovery of the role of normal stromal cells that surround and communicate with these blood cancer cells. Stroma cells are connective tissue cells that can actually release molecules that can make cancers like CLL non-responsive to treatment. Being non-responsive to therapy is one of the main reasons why CLL is so hard to treat. Recently, two new drugs – ibrutinib and idelalisib – performed very well in clinical trials and were approved by the Health Canada in 2014 and 2015, respectively. Ibruitinib, in combination with two other chemotherapeutics used in CLL, was so effective in a Phase III clinical trial– increasing the length of progression-free survival by 80% – that the study was halted early so that all enrolled patients could be treated with ibrutinib. A Phase III clinical trial with idelalisib in combination with one standard chemotherapeutic, increased both overall response (81%, vs. 13% with placebo) and overall survival of patients. These two drugs target the source of the communication between CLL cells and the “normal” cells, so that the cancer cells lose the protection offered by the surrounding tissue and become sensitive to chemotherapy.9 Current clinical trials seek to combine ibrutinib or idelalisib with other chemotherapeutics that will kill the newly sensitized cancer cells.

While both ovarian cancer and CLL are known as hard-to-treat cancers, these new avenues of research will hopefully improve the outcome of many patients in the future. The hope is that CTCs will help to inform treatment plans for ovarian cancer patients, while drugs like ibrutinib or idelalisib will help eliminate a common source of drug resistance for CLL.

This article was written by Ashley Hickman. Ashley is in the second year of a Masters program at the University of Toronto where she studies how to regulate a very important cancer causing gene called myc. To learn more about Ashley and her research check out her bio on our members page. Ashley would also like to thank S. Oppermann at SRI for her valuable input and discussion.

References:

  1. De Angelis, R. et al. Cancer survival in Europe 1999-2007 by country and age: results of EUROCARE-5-a population-based study. Lancet Oncol. 15, 23–34 (2014).
  2. Schmalfeldt, B. et al. Primary tumor and metastasis in ovarian cancer differ in their content of urokinase-type plasminogen activator, its receptor, and inhibitors types 1 and 2. Cancer Res. 55, 3958–63. (1995).
  3. Perez, R. P., Hamilton, T. C., Ozols, R. F. & Young, R. C. Mechanisms and modulation of resistance to chemotherapy in ovarian cancer. Cancer 71, 1571–1580 (1993).
  4. Naumann, R. W. & Coleman, R. L. Management strategies for recurrent platinum-resistant ovarian cancer. Drugs 71, 1397–1412 (2011).
  5. Chudecka-Glaz, A. M. ROMA, an algorithm for ovarian cancer. Clin. Chim. Acta 440, 143–151 (2015).
  6. Resel Folkersma, L., San José Manso, L., Galante Romo, I., Moreno Sierra, J. & Olivier Gómez, C. Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology 80, 1328–1332 (2012).
  7. Allen, J. E. & El-Deiry, W. S. Circulating Tumor Cells and Colorectal Cancer. Curr. Colorectal Cancer Rep. 6, 212–220 (2010).
  8. Robak, P., Smolewski, P. & Robak, T. Emerging immunological drugs for chronic lymphocytic leukemia. Expert Opin. Emerg. Drugs 20, 1–25 (2015).
  9. Rozovski, U., Hazan-Halevy, I., Keating, M. J. & Estrov, Z. Personalized medicine in CLL: Current status and future perspectives. Cancer Lett. 352, 4–14 (2013).
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One thought on “Building New Tools to Fight Stronger Foes: How Research is Making Inroads in the Early Detection and Treatment of Two Hard-to-Treat Cancers

  1. Fergus Huang

    I’m a doctor in Taiwan that focus on CLL treatment and am very interested in this research results. Look forward to talking to you more in the future.

    Like

    Reply

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