New Delhi: Cancer is a disease of uncontrolled cell proliferation in a tissue. Under normal circumstances, cell proliferation and growth is a tightly controlled process that is regulated by the needs of the human body. However, due to certain genetic mutations in key genes that are responsible for regulating this process, proliferation can become uncontrolled and unchecked resulting in a tumour. This tumour can dysregulate several processes in the body to its advantage and can slowly become fatal if not treated. There are several defining characteristics that a cancer possesses, to survive and flourish.
These are known as the hallmarks of cancer. The understanding of cancer up until the early 2000s did not take into consideration the role of the immune system in cancer biology, however later studies showed that the immune system can recognize cancer cells as abnormal/foreign and target them for destruction. However this response has to be specifically activated, and cancer cells can actively suppress this role of the immune system. Hence escape from immune surveillance is now considered an important hallmark of cancer.
What are the treatment options for cancer?
Dr. Urvashi Bahadur, vice president of clinical genomics and Sr. Director of medical genetics and Genomics Strand Life Sciences, said, “The classic methods for the treatment of cancer include surgery, chemotherapy, radiation. While these are the pillars of cancer treatment management, newer modalities are now emerging. Targeted therapy i.e. drugs targeting specific proteins that are activated in cancer, is now a mainstay in the treatment of advanced disease in many cancers. Similarly, with an enhanced understanding of the role of the immune system in cancer, immunotherapy is now emerging as an important treatment modality for solid tumours.
Can immunotherapy help with cancer treatment?
The most common type of immunotherapy in solid tumours is a class called ‘immune checkpoint inhibitors (ICI)’. They work by inhibiting the cancer cell’s ability to repress the natural defense that the body mounts against cancer. Cancer cells have devised a mechanism to prevent the body’s T cells from being activated in response to them and hence escape destruction. This is done by activating an immune checkpoint and is known as immune evasion.
Checkpoint inhibitors work by blocking this inhibitory interaction between cancer cells and T cells. The two most well-studied immune checkpoints are the CTLA-4 checkpoint and the PD1 checkpoint. Ipilimumab is an example of a CTLA-4 inhibitor and there are several PD-1/PD-l1 inhibitors such as pembrolizumab, nivolumab, durvalumab, and atezolizumab. Certain markers can help in deciding whether immunotherapy will be effective. For example, the expression levels of PD-L1, one of the two proteins involved in the inhibitory response, act as a marker for predicting the likelihood of response to these inhibitors.
An additional marker that can be used for assessing the response to checkpoint inhibitors is tumour mutational burden or TMB. TMB is a measure of the immunogenicity of cancer, i.e. how abnormal or different from self does a tumour cell look so that the immune system can recognize it and trigger a response. Tumour Mutation Burden is a measure of the number of mutations that are present in the patient’s tumour, and the larger the number of mutations, the greater the number of abnormal proteins or ‘neoantigens’ produced, and hence more effective is the immune response. TMB can be measured by sequencing large regions of the tumour cell’s DNA. Next-generation sequencing (NGS) is a method that is used to effectively sequence large portions of the DNA and can provide reliable estimates of TMB. A related marker is microsatellite instability (MSI) which is another measure of the mutational load of the tumour. Microsatellite instability is a measure of defective repair of errors in DNA replication and hence indicative of the mutational load of the tumour.
Immunotherapy for solid tumours has proven to be especially useful in certain tumour types such as melanoma, bladder, and lung. Furthermore, while it was initially approved for the metastatic setting, it is also now being used in the adjuvant or neoadjuvant setting, expanding its area of influence. The ICI inhibitor pembrolizumab also has tissue agnostic approval, i.e. it is approved for any solid tumour that has a defect in mismatch repair. However, despite the wide range of tissues and settings in which immunotherapy is applicable, other considerations prevent its widespread adoption, prime among them are tolerability and cost of the medicines. Despite this, the role of immunotherapy in solid tumours is ever-expanding, and dramatic responses have been observed in some patients.
There are several other emerging approaches involving the immune system. Examples include dendritic cell therapy, cancer vaccines, and CAR-T cells. CAR-T cell therapy is effective in heme cancers but is not as effective in solid tumours. Regardless, immunotherapy presents an exciting new arm of cancer treatment, as it harnesses the body’s potential to fight cancer, and it will become a mainstay of cancer management in the years to come.
Cancer as a disease can progress very fast which is why it is important to diagnose the same timely. But the immune system might have a role to play in delaying tumour progression. Health Conditions Health News: Latest News from Health Care, Mental Health, Weight Loss, Disease, Nutrition, Healthcare
