Pillars of Cancer Therapy

Amidst the current initiatives to develop more targeted anti-cancer therapies, immunotherapy has emerged as a highly potent option to selectively eliminate tumor cells with minimal side effects. Immunotherapies essentially make use of the body’s own immune system, or its components, to fight cancer. It is a relatively new concept, currently having achieved pharmacological success with targeted antibody-based therapeutics, including monoclonal and conjugated antibodies. However, over the years, different classes of immunotherapies have emerged for the management and treatment of cancer; these include therapeutic cancer vaccines, oncolytic viruses, cytokines, immune checkpoint inhibitors and certain whole cell-based therapies (adoptive cell therapies).

Cancer treatment has gone through a gradual development process. Surgery is one of the conventional forms of cancer treatment and is still considered to be a vital part of the current standard of care. It is an efficient method to eliminate benign tumors that have not spread to different sites in the body. Surgery is primarily used to remove the entire tumor; however, it very rarely results in a complete cure, since tracing all the sites to which the tumor may have metastasized is difficult.

The advent of radiation therapy was witnessed in 1896 when a German professor, Wilhelm Conrad Roentgen, delivered a lecture, titled Concerning a New Kind of Ray (X-ray). A few months later, methods were devised to use X-rays for the elimination of cancer and soon radiation therapy came into being. Over the years, several developments in radiation physics and computer technology took place, making it possible to deliver radiation more precisely onto tumor sites. However, this type of treatment was shown to cause a number of side effects as well; the cytotoxic radiation used also affected all rapidly dividing normal cells in the target area, leading to various complications post treatment.

During World War I, the Germans used mustard gas as an agent of chemical warfare. Later, the compound was shown to possess potent hematopoiesis suppressor properties. A similar compound, called nitrogen mustard, was found to be effective in treating lymphoma. Soon after, Sidney Farber demonstrated that the use of aminopterin led to disease remission in children with acute leukemia. With time, the use of cytotoxic chemicals, which came to be known as chemotherapy, emerged as a potent cancer treatment option. However, this form of therapy was also associated with its own set of side effects, owing to the harmful effect of the potent chemicals used for this purpose.

Over the past decade, a number of advances in immunology led to a better understanding of the role of the immune system in cancer prevention. As a result, several therapies, aimed to harness the innate potential of the immune system to selectively eliminate cancer cells, have emerged. Cancer immunotherapy is currently classified among the pillars of modern cancer therapies. 

An Overview of Immunotherapies

Conventional cancer treatments, such as chemotherapy, surgery and radiation therapy, have demonstrated very limited efficacy in late-stage cancers. Additionally, chemotherapy and radiation therapy are associated with several side effects. Such treatment options usually destroy large populations of healthy and rapidly proliferating cells, along with the tumor cells. Their non-specific nature has severe detrimental effects on the patient’s quality of life. Therefore, there is an urgent unmet need for innovative and effective cancer treatments for patients with late-stage and refractory cancer. Amidst the widespread initiatives to develop more targeted anti-cancer therapies, immunotherapy emerged as a highly specific and potent option to eradicate tumor cells with minimal side effects. Further, harnessing the underlying potential of the immune system to fight progressive diseases, such as cancer, forms the principle behind immunotherapy. Such therapies aim to educate the immune system with the knowledge of tumor antigens, thereby stimulating its effector to attack those cells that contain specific target antigens. Immunotherapies are known to provide therapeutic benefits by one of the following mechanisms:

• Increasing adaptive immunity
• Decreasing immune suppression
• Increasing T-cell modulation activities

Moreover, immunotherapy may prevent recurrence of tumor post-surgery. The FDA-approved immunotherapies, such as Provenge and Yervoy, represent milestones in the field of cancer immunotherapy for advanced prostate cancer and metastatic melanoma, respectively. Cancer immunotherapy has become an important treatment modality in treating cancer patients with advanced or refractory disease. It is important to mention that this form of therapy involves highly specific targeting capabilities of the immune system. It also has potential applications in the treatment of a vast array of disease indications (other than oncology), including asthma, allergy and Alzheimer’s disease. Cancer immunotherapy was called Breakthrough of the Year in 2013 due to the promising results obtained from the use of genetically modified T-cells to target cancer. The cancer immunotherapy market is currently segmented, featuring the presence of both established players and new entrants. The relatively high efficacy of marketed immunotherapies has further prompted several investors to fund initiatives in this field. Additionally, the existence of numerous unexplored avenues of research has led new players, a mix of both niche and established stakeholders, to enter this market.

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