Targeting Cancer using Biological Therapy

Cancer – the World Health Organization reports it as the leading cause of mortalities worldwide with over 8.2 million deaths in 2012 alone, and millions of more new cases project.

The global health, social and economic burden of cancer and its ever-increasing prevalence has sparked decades of major research, collaborative efforts, and developments to tackle this ravaging disease. Biological treatment in cancer

Over the years, major research and development to tackle the burden of cancer have gained momentum. Apart from detecting cancer in its early stages, great emphasis in newer, more advanced treatment approaches is required, particularly as conventional therapies such as chemotherapy, radiation, and invasive surgery have the disadvantage of harming adjacent healthy tissue, or result in unpleasant side effects. Biological therapy holds the potential solution to unleashing greater (and more improved) treatment approaches for long-term effect, influencing recovery and the lives of many patients.

Although the use of biological therapy is a relatively new and innovative approach in the treatment of cancer, it all began centuries ago (around the late 1700s) thanks to Edward Jenner who pioneered the world’s first vaccine against smallpox. Since then, the method of use of biological therapies has become more refined and better understood, making use of further biological materials such as bacteria, viruses, antibodies and sections of genetic material (RNA or DNA), to name a few.

Today, the use of biological therapy has gained impact and is applied in the field of cancer and autoimmune diseases (rheumatoid arthritis and Crohn’s disease) to name a few, demonstrating high effectiveness compared to conventional therapies. Biological therapy (also called biotherapy or biological response modifiers) involves the use of substances produced in the human body (or animal/ microorganism-origin) or made in a laboratory.

Biological Therapy in Cancer

This form of treatment essentially aims to restore or boost the body’s immune system, control cancer spread or used as a means to overcome side effects of treatment – biological therapy has fewer side effects compared to other cancer treatments. Biological therapy delivers its effective action by abruptly interrupting the very mechanisms that initiate (and maintain) cancer, including cell growth factors, receptors, molecular pathways (EFGR) and angiogenesis (formation of new blood vessels). In addition, biological therapy facilitates the delivery of radioactive isotopes (chemotherapy drugs) directly to tumors. The versatility of current biological treatments places it at the forefront of cancer treatment, improving the quality (and quantity) of life for many patients and with fewer complications.

Biological therapy works with the body’s immune system either directly or indirectly by stimulation or suppression. Immunotherapy and cytotoxic therapy are the two main types of biological therapies. Immunotherapy combines the use of drugs among other methods, creating unfavorable conditions for cancer by acting on the immune system. Cytotoxic therapy, on the other hand, acts on the very mechanisms that keep cancer cells alive, weakening them resulting in apoptosis (cell death). In addition, some biological therapies (targeted therapy) have the capability of targeting cancer cells that evade immune cells.

Types of Biological Treatments

Numerous types of biological treatments exist, such as:

• Monoclonal antibodies (MAbs) – made in the laboratory
• Cancer growth inhibitors – block the growth factors responsible for tumor progression
• Angiogenesis inhibitors – starve tumor growth by disrupting its growth of new blood vessels
• Vaccines – cancer vaccines, for example, identify and target cancer cells
• Gene therapy – using DNA or RNA to repair gene mutations
• Cytokines – interferons, interleukins and tumor necrosis factor (TNF)
• Colony-stimulating factors (CSF) – stimulates red cell production in the bone marrow, lessens side effects of cancer treatments

Selecting an appropriate type of biological treatment relies on the type of cancer the patient has, its stage and preceding treatment. Dosage and length of treatment depend on the type of cancer (and biological therapy) and the patient’s response to treatment; most biological therapies are cytokines and are mainly administered by specific types of injection (subject to the type of biological therapy). Biological therapy usually combines other cancer treatments, such as surgery, chemotherapy, and radiation; in some cases, various biological therapies are combined. Follow-up comprises of numerous tests to determine the efficacy of this tailored treatment approach (modifying dosage if necessary) and whether other treatment options should be considered if required.

Lung Cancer and Biological Therapy

Professor Nir Peled is a world-leading oncologist (and pulmonologist) in lung cancer; he works at various hospitals, such as Herzliya Medical Center, in addition, he has numerous publications that extend on the subject of lung disease, particularly lung cancer.

Lung cancer is one of the most aggressive cancers that exist, symptoms usually only present themselves in the late stages of the disease to which treatment is far more complex. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are the main types of lung cancer, other subtypes also exist, around 85% of lung cancers are NSCLC. Smoking is one of the major contributory causes of lung cancer; others include air pollution, exposure to radon and asbestos, as well as genetic factors.

Conventional lung cancer treatment is non-specific and can cause a series of unwanted side effects and/ or complications. Apart from identifying and screening populations at risk and detecting lung cancer early, delivering an effective treatment protocol (with minimal side effects) is of equal importance. It is for this reason that Herzliya Medical center performs molecular testing among other necessary diagnostic tools, a type of personalized medicine designed to deliver optimum treatment. Molecular testing helps to identify mutated genes or specific proteins, particularly in the advanced stages of cancer. Once identifying these (if any) an appropriate biological therapy can be given and treatment monitored to determine the tumor response (tumor shrinkage) – not all tumors are suitable for biological therapy as some lung cancer patients lack the gene mutations that are known to respond well to targeted therapy.

Biological Therapy at HMC

At Herzliya Medical Center in Israel, biological therapy is widely used, particularly to target cancer. This method has numerous benefits, which include boosting the immune system, slowing tumor growth (preventing metastasis), managing symptoms and reducing the side effects of other cancer therapies. Furthermore, biological therapy has advanced the approach in dealing with metastatic cancer, cancer that has spread from its primary location to elsewhere in the body, for example, metastatic non-small cell lung cancer:

A study conducted by Prof. Nir Peled and his colleagues in the Journal of Thoracic Oncology detailed the presence of a specific gene mutation of the tumor that responded well to treatment. The use of FISH (and immunohistochemistry) identified a specific gene target within ALK (EML4-ALK); scans indicate clearly that patients with metastatic NSCLC with the presence of this mutation responded excellently to the treatment Crizotinib. The patient noticed the results of treatment within 2 weeks, noting a reduction in pain in the pubic area and an improved tolerance in exercise. After 4 months of treatment, imaging scans of CT and PET proved phenomenal – PET scan was negative, and the CT scan revealed tumor shrinkage. Imaging results are depicted below (A-chest, B-pelvic region), the arrows point to the tumor region.

Biological treatment in (lung) cancer

In addition, this mutation EML4-ALK is found in neuroblastomas and some other cancers, suggesting it as an effective target in cancer treatment.

Herzliya Medical Center analyzes lung cancer in a comprehensive manner, taking into account the patient’s needs, performance, and health status. Oncologists then profile the disease and tailor the most appropriate therapy according to the patient’s status. The use of bimolecular histological analysis (of the tumor) combined with biological therapy has increased the life expectancy of patients by more than 50%, late-stage (advanced) lung cancer patients’ average survival rate was around 4 months – it is now around 3.5 years. Treatment may include drug therapy specifically designed to target the EFGR gene, ALK, ROS, RET and more, or combined with cutting-edge immunotherapies, results of tumor shrinkage can be observed 3-4 months following treatment.

Continued research and the identification of further molecular targets in tumors, hold the key in unleashing revolutionized treatment not just in cancer, but other diseases as well.