Novel Therapies for Cancer

Table of Content

• What is Cancer?

• Types of Cancer

• What are Conventional Therapies for Cancer?

• What is Novel Therapy?

• Novel Therapies for Cancer

• Take-Home Points

• FAQ on Novel Therapies for Cancer

What is Cancer?

Cancer is the uncontrolled growth of cells in the body. The body always replaces the older cells or regenerates the dead or injured cells by creating new cells through a process called cell division. Cell division is a regulated process, there are several genes and proteins which are responsible for regulating the cell cycle, cyclin being one of them so that cells will divide only when necessary. The basic crux of cancer is that the process of cell division becomes uncontrolled. The uncontrolled division of cells can be due to mutations in genes which code for proteins necessary to regulate the cell cycle.

How does Cancer Originate?

• Cell division is a controlled and regulated process in the body. 

• There are proteins which check for DNA mutation at each level of the cell cycle or division, if any mutation is detected, the cell cycle stops. 

• Contrary to that there are other proteins which help cells to synthesize the required ingredients so that they can grow and divide themselves, in simple words, they promote cell division. 

• So basically, two groups of proteins are involved in controlling cell proliferation. The body cannot afford any disruption in this process. Whenever there is a disruption in these processes, other mechanisms like apoptosis which is cellular suicide, become active and the cell immediately dies, this mechanism is developed in cells so that cancer cannot develop.

• Uncontrolled proliferation starts, immediately apoptosis begins and boom the cell dies. 

• For the development of cancer, both of these mechanisms must be deranged, the regulation and the apoptosis. Although there are many more complex processes involved in the development of cancer, this will help for our purposes. 

• For Cancer three things needs to happen, first upregulation of the regulatory process which is promoting cell division, then downregulation of processes which are inhibiting cell growth, and lastly the cell must escape apoptosis, because if it does derange the first two regulatory mechanisms then it also apoptosis prevents it from uncontrolled proliferation. One cell starts uncontrolled proliferation and then produces daughter cells which also inherit the quality of the first cell i.e, uncontrolled proliferation. 

• Daughter cells divide and give rise to more cells and this process goes on eventually, the patient develops a mass of cells which are continuously dividing very rapidly and invade the surrounding tissue, this whole thing we call “cancer” or “tumour”.

Types of Cancer

1. Based on invasive property

• Cancer could be benign or malignant. Benign cancers do not spread from place to place, they are localised and are generally safe and cause no harm. 

• Lipoma is one of the most common benign tumours that one can get. In contrast to that malignant tumours or cancers have the property of metastasis. Metastasis simply means they can invade the body and can walk around and invade any tissue or organ of the body. 

• The problem with cancer cells is that they don't just proliferate and metastasize but in the cell division process they consume the food of other cells, making the normal cells starve to death. This is one of the ways cancer cells harm the body.

•  There are many other complex pathways taken by cancer cells which cause damage, but simply this will help.

•  Metastasis makes the problem worse; these cells can move anywhere and can invade and deprive any organ deprived of food.

2. Based on the organ/tissue involved

Based on the tissue involved, cancer is named accordingly and some cancers are more dangerous than others depending on how important the organ is to the body and how much metastasis takes place from cancer of that tissue. The nomenclature is quite straightforward when the breast is involved it is named breast carcinoma, cancer of the pancreas is pancreatic carcinoma and so on, Sometimes the suffix “-oma” is used depending on the tissue of origin like lymphoma is cancer of white blood cells, one of the components of blood.

What are Conventional Therapies for Cancer?

1. Surgery

Treatment of cancer using surgical procedures is quite old, excision of the tissue which is proliferating is done and is taken out. This is only possible when the cancer has not yet metastasized. Most of the time some cancerous cells are left behind, and the chances of leaving a few 100 cells are quite high since the surgeon cannot see cells, they are microscopic. Sometimes adjuvant therapy is used before surgery. If the cancer size is big then firstly using chemo it is shrunk and then excised.

2. Chemotherapy

Chemotherapy drugs kill those cells which are dividing continuously, conventional chemotherapy kills all the cells which are dividing rapidly irrespective of whether they are cancerous or not. Therefore people who are going through chemo experience hair loss, and vomiting because hair cells and gastrointestinal cells also divide continuously. 

3. Radiation

Radiation uses ionizing and non-ionizing rays to kill cancer cells without surgery. It also has limitations as radiation damages peripheral tissue. Most of the time a combination of these three is used. Targeted therapies for cancer are not achieved by conventional treatments for cancer. There is a need for targeted therapy, this is what is achieved by novel therapies for cancer treatment.

Disadvantages of Conventional Therapies for Cancer

A side effect of chemo comes from the fact that it damages the cells of the body also, and the growing healthy cells of the body get damaged. Other side effects include:

• Lethargy

• Hair loss: cancer chemo attacks the growing cells of the body, therefore hair loss is a common side effect

• Decreased immunity

• Reduced appetite

• Sometimes a sore mouth

• Vomiting post-chemotherapy.

• Diarrhoea 

• Can cause long-term damage to the heart, lungs, kidneys etc.

Most of the symptoms go away in a matter of hours or days or months but some may last for years.

What is Novel Therapy?

• Novel therapies mean treatment procedures which are developed recently. Novel cancer therapies are focused on targeting only those cells which are cancerous and giving less damage to normal cells. 

• Novel therapies like immunotherapy are targeted approaches to curing cancer killing only cancerous cells.

• There are different types of novel therapies some of the important ones include:

1. Immunotherapy

2. Monoclonal antibodies

3. Biotechnological drugs

4. Anti-cancer vaccines

How Novel Therapies Originated?

The first breakthrough in the development of can therapies came in the 1980s when molecular and cell biology techniques led to the development of specific drugs for specific cancers. Both chemotherapy and targeted therapy got a boom. 

The second breakthrough came because of genetic engineering, when antibodies-based therapy is introduced, antibodies protect us from diseases. These antibodies are called monoclonal antibodies. Immunotherapy is one of the novel therapies for treatment that is popular nowadays.

They can be used to treat advanced cancer which is at the last stage. Subsequent treatment from these has been shown to improve the patient's condition.

Nowadays, cancer research is focused on anti-cancer vaccines and technological drugs which have been shown to work great on animal testing.

Advantages of Novel Therapies over Chemotherapy

• Novel therapy like immunotherapy doesn't itself harm cancer but increases our body's ability to fight cancer. In contrast to chemo which is toxic to the body and kills cancer by itself.

• Immunotherapy continues the fight against cancer even when the treatment is stopped. While chemotherapy stops working when treatment is stopped.

• Immunotherapy acts as targeted therapy, therefore it doesn't kill our cells as chemotherapy does.

Disadvantages of Novel Therapies like Immunotherapy

• Chemotherapy is less costly than immunotherapy.

• Immunotherapy although has very few side effects compared to chemo since we give power to our immune system to kill cancer, sometimes the immune system gets over-activated and starts damaging our organs.

• Immunotherapy although it has fewer side effects one limitation is that when side effects arise they don't subside even after stopping the therapy.

• In Chemotherapy, more severe side effects arise but they resolve when the treatment is stopped.

Novel Therapies for Cancer

1. Drugs Inhibiting Enzymes

Enzymes are molecules which are involved in different processes which the cell performs for its survival. Enzyme inhibitors are one the best novel therapies for cancer treatment. Targeted killing of cancer cells is done.

• Farnesyl transferase inhibitor

  This blocks the signals which are telling cells to grow and become cancerous thereby stopping the growth of cells.

• Cyclin-dependent kinase inhibitors

Cyclin protein as discussed above promotes cell growth. Cancer cells over-express these proteins and this drug blocks cyclin activity by blocking their enzyme.

• Proteasome inhibitors

Cancer cells while growing produce a lot of proteins and excrete these out of the cell or degrade them. Proteasome is a molecule which throws these proteins out of the cell. The blocking the action of this molecule leads to the accumulation of proteins inside cancerous cell and ultimately killing them.

• IMP Dehydrogenase inhibitors

IMP Dehydrogenase enzyme is required for DNA synthesis. DNA is the blueprint of cells which is required by all the cells to grow and divide and so is required by cancer cells to divide. So by inhibiting DNA synthesis these drugs stop the growth of cancer cells.

• Histone deacetylase inhibitor

Histone is a protein on which DNA wraps and gets stored in cells. This drug destroys HISTONES and ultimately damages DNA thus impairing cancer growth.

2. Receptor Antagonists 

Growth signals are hormones which are present in our body and tell the normal cell that you have to live, don't die but grow in your population. Cells need constant stimulation of growth signals from our body to survive and live, these block these growth signals. This class of novel therapies for cancer again is targeted treatment of cancer.

• Endothelin receptor antagonist

• Retinoid agonist

Retinoid signals are a form of growth signals necessary for the regulation of cell growth and act as police which regulates everything. Agonist means they stimulate these receptors. Since they are stimulating these, our police become more strong and control the growth of cancer cells.

3. Tyrosine kinase Inhibitors

Tyrosine kinases are enzymes which activate genes that act as “on” and “off” switches, when a gene is on a cell will divide, in a normal cell it gets off after some time but In Cancer cells are turned on and don't get off. These drugs off the genes so that cancerous cells don't grow.

Tyrosine kinase inhibitors include

• Epidermal Growth factor receptor inhibitor

• Anti-angiogenic factors

• BCR-Abl inhibitor

• Janus kinase 2 inhibitors

• SRC tyrosine kinase inhibitor

4. Monoclonal Antibodies

Monoclonal antibodies as novel therapies for cancer have come as newer development in curing cancer. Cancer cells express a variety of proteins that are specific to them, and monoclonal antibodies target these proteins and destroy cancer cells. They are the most targeted approach to curing cancer.

5. Carrier Systems

Carrier systems as novel therapies for cancer treatment is not a drug but it is transport mechanism that is used for transferring the drug to tumour cells, and this technique doesn't spread cancer drugs to the whole body which are toxic to cells, but they only deliver drugs near the cancer cells.

The Carrier system includes

1. Solubilisers

2. Implantable carmustine wafer

3. Nanotechnology

4. Polymer drug conjugates

5. Pegylation

6. Liposomes

7. Proteins and amino acids

Take-Home Points

• Cancer is the uncontrolled proliferation of cells, and normal regulatory mechanisms of cell cycle and division are deranged in cancerous cells.

• There are two types of cancer: benign and malignant. Benign tumours are relatively safer than malignant tumours as they do not metastasize.

• Conventional therapies for cancer treatment are non-specific and include surgery, radiation and chemotherapy.

• Chemotherapy has some side effects, common ones include lethargy, vomiting, hair loss, and decreased immunity.

• The cost of immunotherapy is far higher than chemotherapy.

• Novel therapies for cancer are more targeted and use different growth signal modulators and enzyme inhibitors.

• Novel therapies include immunotherapy which doctors are utilizing to give targeted treatment to cancer patients.

• Novel therapies for cancer treatment also include a carrier system which itself is not a drug but carries anti-cancer drugs to sites where cancerous cells are present, serving as a targeted approach while dealing with cancer.

References

• https://www.sciencedirect.com/science/article/pii/S0149291816301631

• https://aacrjournals.org/clincancerres/article-abstract/14/5/1310/179797

• https://www.jstor.org/stable/24993349

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243123/