Evolving treatments of cancer: From remission to cure

The medical history of cancer began millennia ago. Historical findings of patients with cancer dates back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery, which was ineffective, leading to death of patients. Despite advances in the diagnostic, medical and interventional fields, the number of new cases of cancer are increasing every year.

Over the centuries, important medical discoveries have allowed to identify the biological and pathological features of tumors. This however did not contribute to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the first modern therapeutic approach in medical oncology. A real breakthrough took place after the Second World War, with the discovery of cytotoxic anti-tumor drugs (chemotherapy) for the treatment of cancer. Since then, there has been an exponential growth of studies concerning the use of new drugs for cancer treatments.

The second fundamental breakthrough in the field of oncology and pharmacology took place at the beginning of the 1980s with the molecular and cellular biology studies, which allowed the development of specific drugs for the molecular targets in cancer, giving rise to the targeted therapy. Both chemotherapy and targeted therapy have significantly improved the survival and quality of life of most of the cancer patients inducing complete tumor remission. Unlike the classic chemotherapy approach, which acts on both normal cells and cancer cells, the targeted therapy and new selective inhibitors are able to affect only cancer cells with minor side effects toward the normal cells.

Cancers that respond to treatment are not considered as outright cured, because there is always a potential that they could come back. Instead, they are referred to as being in complete remission (CR), meaning there is no detectable cancer in the body at that time. In terms of what the future holds for curing cancer altogether, some experts believe that the evolving treatments may, one day, make this a reality.

Cancer cells often find ways to escape both treatments and the immune system. Cancer is a disease, which evolves as it progresses, meaning that late-stage cancers can become very hard to treat successfully. Cancer cells continually change and acquire new mutations. These new mutations may give rise to new characteristics, such as the ability to spread more freely. Such changes in cancer cells mean that a tumor that responded to treatment at first, has found ways to resist cancer drugs and continue to grow.

With the recent developments in genetic engineering, there is a further advancement of onco-pharmacology with the introduction of monoclonal antibodies and immune checkpoint inhibitors for the treatment of even advanced tumors, for which no effective treatment was available before.

Currently, several researchers are focused on the development of cell therapies, anti-tumor vaccines, and new bio-technological drugs that have already shown promising results. Therefore, in the near future, we will certainly see a new revolution in the field of oncology treatments. Among these, monoclonal antibodies and new immunotherapeutic drugs have allowed the development of new personalized therapeutic protocols (personalized medicine). These strategies have significantly increased the effectiveness of treatments and the survival rates of cancer patients with low toxicity for patients. Even if cancer cannot be considered 100% eradicated today, many can be effectively "cured" if detected early. A child with acute lymphoblastic leukemia after treatment if reaches remission, will be considered as cured as the likelihood of recurrence after successful treatment is low.

Many targeted therapies are able to control the growth of a tumor for a time before the resistance develops. In some cases, next-generation drugs are available that allow people to stay ahead of this resistance, but tumors often change again. Resistance also can transform a tumor into a completely different subtype of cancer. The ability to identify gene mutations and rearrangements is expanding. Tests such as Next-Generation Sequencing (NGS) allow healthcare providers to examine many genetic alterations that may be treatable.

Newer tests like Next Generation Flow (NGF) cytometry and next generation sequencing (NGS) further helped to detect presence of disease at a very low level and helped to continue treatment until we reach a state of undetectable disease or use newer agents to get to the undetectable stage. For example, Multiple myeloma a bone marrow cancer, at diagnosis will have 10:12 cancer cells. After treatment when we say that patient achieved Complete Remission (CR), patients still have 10:08 cancer cells, which is a very high number. This is the cause of recurrence of cancer. Use of above tests to detect cancer at a very low level and use of newer medicines to reach an undetectable disease state, has let to deeper responses and potentially reduced the chances of recurrence. This has allowed patients to reach the possibility of 'potential cure'.    

Targeted therapies, while not a cure, can sometimes control a cancer for a significant period. Imatinib used to treat chronic myeloid leukemia is a good example. Here patients control their cancer as a chronic disease much like blood pressure.

The immune system knows how to fight cancer with powerful cells such as T cells. Unfortunately, cancer cells have discovered the ability to suppress that immune response and hence cancer cells can grow unchecked. Immunotherapy drugs work to empower the immune system instead. Immunotherapy drugs known as checkpoint inhibitors make cancer cells visible to the immune system. Immunotherapy in combination with chemotherapy and radiation treatment can improve control of cancers. Combination protocols, which use different types of treatments, can increase the treatment efficacy and reduce the possibility of developing pharmacological resistance.

Allogeneic Bone Marrow Transplantation (BMT) provides a new immune system from a related or an unrelated donor, which fights cancer and provides cure in nearly 70% of patients. Although this is a relatively toxic treatment procedure with several post-transplant complications, surviving patients can live without cancer for rest of their life.

The discovery of new and effective therapeutic strategies, including the Chimeric Antigen Receptor (CAR-T) Cell therapy and gene therapy has been effective in reaching to the state of cure. During CAR-T cell therapy, T cells are extracted from a patient's blood, programmed to recognize a specific cancer cell antigen, and then reinfused to the patient. These engineered T cells then expands in number in blood and kill the cancer cells. This new era of cellular therapy has made revolution in cancer treatment, particularly in blood and bone marrow cancer treatment. This has provided potential cure for cancer patients who were otherwise not suitable for remission or cure with other modalities of treatment.

Advances in cancer treatment are not the same as a cure, but they are helping people to live longer with a cancer, sometimes even with the hope of managing it as a chronic disease. Evolving research continues to deliver more personalized care, including immunotherapy and targeted therapy drugs. Advances in allogeneic bone marrow transplantation and new therapies like CAR-T cells therapy and cellular therapies offer options that were not possible a few years ago, with potential towards cancer cure soon.

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