Abstract

Lung cancer in non-smokers (LCINS) contributes to 10-20% of lung cancer cases per year (NCI, 2021). Scientists agree that LCINS is caused by exposure to environmental factors (NCI, 2021). Traditional treatments, such as chemotherapy, radiotherapy and surgery, have had a long history of success. Modern and emerging treatments, such as gene therapy, stem cell therapy and targeted drug therapy, yield small rates of success but high promise (Medline Plus, 2023).  

Chemotherapeutic drugs, like carboplatin or pemetrexed, are highly efficient but regard numerous side effects that, in many cases, result in lesser use on varying patient types (Cancer Research Uk, 2024). Similarly, in radiotherapy, tumours are precisely targeted using effective techniques, such as stereotactic ablative radiotherapy, but can result in detrimental side effects (Stanford Health Care, 2024). Surgery is the most common traditional technique with side effects being comparatively minimal, though the procedure doesn’t eliminate the possibility of a returning cancer (American Cancer Society, 2019).

Gene therapy restores mutated factors that contribute to the rise of cancerous cells, such as the tumour suppressor gene TP53 (Mayo Clinic, 2024). In contrast, stem cell therapy induces mesenchymal cells, which can travel along the bloodstream to self-destruct and eliminate large amounts of cancerous cells. These treatments, while effective, are easily susceptible to complications and harmful/lethal side effects (Tee-Melegrito, 2021).

This review aims to compare the modern and traditional treatment for LCINS. Existing research for LCINS treatment is primarily clinical trials, which aim to determine the most efficient form of treatment. In this review, both modern and traditional treatment efficiency, side effects, and comparative benefits/risks were considered. It was concluded that a combination of radiotherapy and chemotherapy would prove most effective while still considering a development of modernised treatments for future treatment.

1. Introduction

Historically, lung cancer has been predominantly associated with tobacco smoking (Medline Plus Genetics, 2017). Lung cancer is often viewed as a smoker’s disease while, in actuality, approximately 10-20% of lung cancer cases are in non-smokers (NCI, 2021). Typically, the type of lung cancer diagnosed in non-smokers is non-small cell lung cancer (Nall, 2023). Non-small cell lung cancer is differentiated from small cell by its aggressiveness. Non-small cell lung cancer is less aggressive in comparison to small cell lung cancer (SCLC), despite its greater rate of occurrence.

Non-small cell lung cancer (NSCLC), can be further sub-categorised as squamous cell carcinoma, adenocarcinoma or large cell carcinoma (Nall, 2023). The most prominent type being adenocarcinomas, which is commonly found in females (Samet, 2013). LCINS is caused by numerous factors, such as second hand smoke, radon, air pollution, asbestos, family history of lung disease or previous exposure to respiratory disease leading to susceptibility in the lungs (Samet, 2013). These factors are often referred to as carcinogens. The most prominently occurring cause for NSCLC is second hand smoke (American Cancer Society, 2024). Carcinogens in lung cancer cause mutations in somatic cells and tumour suppressor genes, such as TP53, EGFR, and KRAS, allowing for uncontrolled cell division (Medline Plus Genetics, 2017). The TP53 gene is a specific tumour suppressor gene which regulates the rate of protein and gene division. The EGFR gene regulates the function of cells in the lining of the lungs. Finally, the KRAS gene is a proto-oncogene that, prior to mutation, controls cell signals of cell division regulation to the nucleus (NCI Dictionary of Cancer terms, 2024). As NSCLC progresses, it becomes more difficult to treat. In some cases, benign tumours, after the absence of treatment, become malignant and spread to other areas of the body. At this point, the cancer spreads too rapidly to be treated (Cleveland Clinic, 2023). 

Traditional treatments for NSCLC include: surgery, chemotherapy and radiotherapy. Recently there have been developments for new types of treatment such as gene therapy, stem cell therapy and targeted drug therapy. This paper will explore and compare traditional and emerging types of treatment to establish the most beneficial form of treatment for NSCLC.

2. Traditional Treatments for Lung Cancer in Non-Smokers

2.1 Chemotherapy

Chemotherapy involves prescribing a drug, or a combination of multiple drugs, taken orally or intravenously, to kill cancer cells and prevent them from dividing. It is a traditional and effective way to treat cancer, showing a 13% decrease in risk of death in NSCLC patients (BMJ, 1995). Some of the most common chemotherapeutic drugs used to treat SCLC and NSCLC include: cisplatin, carboplatin, etoposide, pemetrexed, gemcitabine, paclitaxel. Of these chemotherapeutic drugs, carboplatin and pemetrexed are used together to treat NSCLC and pleural mesotheliomas (Cancer Research UK, 2024).

2.1.1 Carboplatin

Carboplatin is a cytotoxic chemotherapeutic drug that is derived from cisplatin, but exhibits a lower toxicity in SCLC patients (Ettinger, 1998). In a phase II trial, it was used in combination with etoposide and vincristine, which led to remission in 84% of patients in early stages of cancer (Gatzemeier., Hossfeld et al., 1991). Carboplatin is a new platinum-containing compound that is derived from cisplatin. Cisplatin has shown similar survival rates, but its toxicity and associated side-effects are more significant than carboplatin (Ettinger, 1998). The most common side effects associated with carboplatin are temporary reduction in production of red blood cells in the bone marrow, which leads to temporary anaemia and tendency to bruise, increased risk of developing infections, nausea and vomiting, and loss of appetite (Cancer Research UK, 2023). Carboplatin can also cause diarrhoea, alopecia and hearing problems (Cancer Research UK, 2024). Some side effects like nausea can be mitigated by use of drug therapy. Not eating before treatment may help relieve the risk of vomiting, and changes in diet, such as eating several small meals or limiting activity, may help lessen some of these effects.

2.1.2 Pemetrexed

Pemetrexed is an antifolate used to treat late stage non-squamous NSCLC. A lower rate of hematologic toxicity was observed in patients treated with pemetrexed (Al-Saleh, 2012). There are over 400 clinical trials being carried out to investigate the efficacy of pemetrexed against non-squamous NSCLC (Tomasini et al., 2016). The Food and Drug Association (FDA) have approved the use of pemetrexed in multiple steps of treatment of nonsquamous NSCLC (Gyawali B., et al., 2018). Pemetrexed is one of the most frequently used cytotoxic chemotherapy agents for treating stage IV nonsquamous NSCLC (Tomasini P., et al., 2016). Pemetrexed inhibits cell replication and growth through the inhibition of three enzymes involved in purine and pyrimidine synthesis: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase (Al-Saleh., 2012). Pemetrexed inhibits deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, needed for cell growth and survival (Tomasini et al., 2016). Pemetrexed is also commonly administered in combination with cisplatin or carboplatin, which are platinum-based chemotherapeutic compounds. Results from a phase III study have proven that a combination of cisplatin and pemetrexed was superior to a combination of cisplatin and gemcitabine to treat adenocarcinomas, the most common type of tumour occurring in non-smokers (Tomasini et al., 2016). A randomised phase II study of pemetrexed versus placebo after first-line chemotherapy with cisplatin–pemetrexed indeed showed promising results in terms of progression-free survival (PFS) (Tomasini et al., 2016). Some side effects of pemetrexed include increased risk of infections, breathlessness, diarrhoea or constipation, loss of appetite and mouth ulcers and in fewer cases, patients can get alopecia, dizziness or other side effects (Cancer Research UK, 2022).

2.2 Radiotherapy

Radiotherapy at high doses can kill or prohibit the growth of cancer cells by damaging their DNA, which ends their cell cycle, allowing them to be killed and broken down by the body. This process is slow and requires days or weeks of treatment until the first effects are observed (National Cancer Institute, 2019). Radiotherapy can be segregated into two main types: external beam and internal (National Cancer Institute, 2019).

Radiotherapy can be used as the main form of treatment, or supplementary to surgery, to improve prognosis (American Cancer Society, 2024). It can also be used for palliative purposes. The most common types of radiotherapy used to treat NSCLC are external beam radiation therapy (EBRT), brachytherapy and proton therapy (American Cancer Society, 2024). External beam radiation therapy is a fast and painless procedure that involves focusing radiation from an external source onto the tumour from outside the body. Most often, radiation treatments for lung cancer are administered five days a week for 5-7 weeks, with variation based on the type of EBRT and the tumour (American Cancer Society, 2024) . The invention of newer procedures that cause smaller exposure to radiation to healthy cells is helping doctors treat lung cancer more efficiently (American Cancer Society, 2024). Some of these new techniques include stereotactic ablative radiotherapy (SABR), which is mostly used to treat cancer in its early stages. As well as three-dimensional conformal radiation therapy (3D-CRT) that digitally locates the tumour to improve the precision and accuracy, increasing the efficacy of the treatment (American Cancer Society, 2024). Brachytherapy is used to shrink airway tumours and to relieve symptoms (American Cancer Society, 2024). This treatment involves inserting a small radioactive source into the airway or into the tumour using a bronchoscope, and in some cases, surgically. In most cases the source is removed shortly after placing it, but it may be left in for longer depending on factors such as the size or type of the tumour. Proton therapy involves firing protons (positively charged particles) at the tumour. Proton therapy is often used to treat later stages of NSCLC (American Cancer Society, 2024). Some of the most common symptoms associated with radiotherapy include fatigue, nausea, vomiting, alopecia and skin changes specific to the site of treatment. Some symptoms can be managed by maintaining a balanced diet and healthy lifestyle (Schlembach, 2017).

2.3 Surgical Interventions in NSCLC

In cases of NSCLC, surgery is typically carried out as treatment in the early stages of development. Surgery can be complex, and is often carried out by a thoracic surgeon. Lung cancer surgery involves either the removal of a part of a lung, or the entire lung, known as a lung resection. There are many types of lung resections including: pneumonectomies, which involve removal of an entire lung; lobectomies, which involve removal of the cancerous lobe/lobes; wedge resections, which involve removal of the cancerous part of a lobe; and sleeve resections, which involve resection of tumours in the large airways of the lungs (American Cancer Society, 2024). The type of lung resection performed is decided by considering the size and location of the tumour, and the patient’s pulmonary function. There are also multiple surgical approaches that can be taken to carry out the surgery. The two main approaches are thoracotomies and minimally invasive approaches. A thoracotomy is an open lung surgery, during which the thoracic surgeon makes a large incision between the ribs to access the site of the tumour (American Cancer Society, 2024).

There are two main types of minimally invasive approaches: video-assisted thoracic surgery (VATS) and robotic-assisted thoracic surgery (RATS). VATS is more commonly used to treat lung cancer in its early stages. It requires a smaller incision, and requires less time spent in recovery after the procedure (American Cancer Society, 2024). RATS involves assistance by a robot. The surgeon controls the robot from a panel in the operating room. The robot carries out the procedure through small incisions on the chest. It can be preferable to a thoracotomy as it has a relatively shorter recovery time, and causes less pain and blood loss (American Cancer Society, 2024). It also allows the surgeon to be more precise using the robotic arm. The surgical procedures used to treat lung cancer are complex procedures, and come with a set of risks and possible complications. Among these, some of the possible complications include: wound infections, adverse reactions to anaesthesia, blood clots or excessive blood loss (American Cancer Society, 2024). Recovering from invasive procedures like thoracotomies takes weeks, even months if there are complications. Minimally invasive procedures reduce recovery time, and also reduce some risks, like wound infections, as they require smaller incisions (American Cancer Society, 2024). Recovery time is also influenced by the condition of the patient’s lungs, and type of tumour and procedure. 

3. Modern and emerging approaches for treating lung cancer in non-smokers

3.1 Gene therapy

The most common types of genes that are altered or genetically mutated to cause cancer are proto-oncogenes and tumour suppressor genes (Humberto et al., 2017). Proto-oncogenes are genes that have the potential to cause cancer when mutated or abnormally expressed (American Cancer Society, 2022). Tumour suppressor genes are genes that regulate the cell cycle. However, when there is a mutation to the gene, such as a missense mutation or base substitution, the function of the gene changes and becomes inactivated, causing the lack of regulation which leads to uncontrolled cell division. 

Although still in clinical trials, gene therapy proves potential for treating lung cancer (Humberto et al. 2017). This potential is demonstrated by efforts to restore activated tumour suppressor genes or activate the tumour suppressor genes in the patient to better regulate the cell cycle and regulate uncontrolled cell division (Humberto et. al, 2017).

The P-53 gene is a common example of a tumour suppressor gene and is extensively studied (Humberto et. al, 2017). Retroviral vector is a biomedical laboratory technique that involves the permanent integration and insertion of specific lipid-enclosed particles into the genome of mammalian cells. Through retroviral vectors, functional and activated p-53 genes are inserted into the genome of human non-small cell lung cancer (NSCLC) cells. Results show suppression of some NSCLC cells in vitro, proving the usage of gene therapy in terms of restoring tumour suppressor genes promising as it slows the growth of cancer cells. The insertion of tumour suppressor genes into patients on first line treatment, who have not had any other treatment resulted in reduced tumour size by 50% (Dresden, 2021). The usage of this tumour suppressor gene therapy is also proven to be even more effective when combined with other therapies such as chemotherapy or immunotherapy (Humberto et al. 2017).

The usage of gene therapy in NSCLC, specifically, is shown to be promising where a study of 17 patients with localised NSCLC were given treatment of p53 gene transfer in conjunction with radiation therapy. The overall response rate was 5 out of 17 (29%) and response rate of the local injected side was 9 out of 17 (52.9%); meanwhile the overall survival rate at one year was 56% (Moon et al., 2003). However, the usage of gene therapy raises ethical concerns about the therapy being a tool to alter human nature and restricting freedom of choice by predetermining a person’s life. An ethical concern of gene therapy is that it can be exploited in a eugenics movement, which will reject any imperfections given current society values physical beauty, intelligence and a long life, resulting in lack of uniqueness among the population (Penticuff, 1994). There is also a risk of genetic profiles being known to potential employers and insurers as it becomes more integrated in treatment, which could result in discrimination and a loss of privacy (Penticuff, 1994).

3.2 Stem cell therapy

Stem cells are clonal cell populations that derive from single cells and originate in the bone marrow, with the ability to self-regenerate and differentiate into other cell types (Lu Lv et. al, 2023).

Stem cell research reveals a lot of potential in treating diseases, revealing usage in myocardial infarction, acute respiratory distress syndrome and liver injury (Lu Lv et. al, 2023). Mesenchymal stem cells are adult stem cells with the ability to differentiate into different cell types and are taken from the bone marrow, blood of the umbilical cord and peripheral blood carrying various minerals throughout the bloodstream in and out of vital organs such as the heart, fallopian tube tissues, foetal liver tissues and lung tissue (Lu Lv et. al, 2023). Mesenchymal stem cells were also revealed to have the potential ability to specifically localise tumours, as well as metastatic tumours, but is still under research (Lu Lv et. al, 2023). Metastatic tumours refer to tumours that have been formed through the metastasization of primary tumours to other locations in the body. Mesenchymal stem cells (MSC) have also been shown to have effective use in treating degenerative illnesses in both clinical and preclinical trials with MSCs taken specifically from the bone marrow having the ability to deliver anticancer drugs (Lu Lv et. al, 2023).

MSCs expressing tumour necrosis factor-related apoptosis-inducing ligands (TRAIL) can migrate to tumours and cause the apoptosis of lung cancer cells, reducing the growth and metastasization of primary tumours (Loebinger et. al, 2010).  Tumour necrosis factor (TNF) is a cytokine that is responsible for a wide range of signalling cascades such as cell survival, differentiation and apoptosis which is produced by macrophages and monocytes (Wang et al., 2009). Hence TRAIL are ligands that are expressed by stem cells and specifically induce apoptosis in cancer cells (Loebinger et al., 2010). Stem cell therapy also works in combination with chemotherapy to induce apoptosis effects on tumours and helps prevent cancer (Loebinger et. al, 2010). However, more clinical trials need to be done on TRAIL expressing stem cells in lung cancer treatment and is still considered in the experimental phase.

There is a caution that comes with using stem cell therapy for lung cancer as it has not been studied in depth specifically in patients with lung disease (American Lung Association, 2024). Hence, despite the variety of sources that stem cells can be extracted from, it currently does not have much potential for treating lung cancer, therefore more clinical trials will need to be done. Other than the lack of trials, there are current ethical controversies focused on the unlimited differentiation potential of stem cells which can be used in human cloning, posing a risk of generating human embryos (Volarevic et al., 2018).

3.3 Gefitinib

Gefitinib is a type of tyrosine kinase inhibitor that comes as a tablet and is taken orally. Tyrosine kinase inhibitors are a group of biochemical agents that disrupt the signal transduction pathways of different protein kinases through different modes of inhibition, which helps disrupt the signalling of kinases that directly contribute to the formation of cancer (Thomson et al., 2023). Gefitinib specifically inhibits protein kinase, epidermal growth factor receptor (EGFR) (Kris et. al, 2003). EGFR is a receptor protein and protein kinases involved in cell signalling pathways that control cell division and is found on the surface of many cells on the body. A conformational change is caused when a ligand binds to the EGFR receptor protein, which activates the receptor protein’s kinase domain and allows EGFR to undergo phosphorylation (the addition of phosphate groups) at specific tyrosine residues (Rayego-Mateos et al., 2019). Through phosphorylation of EGFR, docking sites are created for other signalling molecules triggering a cascade of events within the cell and ultimately leading to various cellular responses such as increased cell proliferation and growth (Rayego-Mateos et al., 2019). The phosphorylation of EGFR is powered by ATP, in which there is an ATP binding cleft within the kinase domain of EGFR. As ATP binds to the cleft, there is an energy source that fuels the phosphorylation reactions for causing the cascade of cellular response events (Kumar et al., 2008).

Mutations in the receptor protein may induce further signalling pathways continuing the division of cells, causing more cells to be produced than normal and ultimately leading to cancer. With its inhibitory properties, gefitinib would bind to the ATP binding cleft of the EGFR, preventing ATP from binding to the cleft and giving the receptor protein an energy source for the phosphorylation reactions and hence the creation of docking sites to trigger various cellular responses (Pedersen et al., 2005).  Hence, gefitinib restricts the energy source of EGFR, stopping it from triggering signalling cascades. 

The usage of gefitinib for treating lung cancer is effective, with the drug being especially effective in non-smoking lung cancer patients (Lim et al., 2005). A recent study showed that symptoms of NSCLC improved in 43% of patients who received 250mg of gefitinib and in 35% of patients who received 500mg of gefitinib; benefits were observed within three weeks in 75% of patients (Kris et al., 2003). However, the usage of gefitinib comes with common side effects such as loss of appetite and sore mouth or throat (Macmillan Cancer Support, 2022). A life-threatening but rare side effect is interstitial lung disease (Hong et al., 2016).

4. Comparing traditional and modern treatment types

To consider the extent to which either treatment type is more significantly beneficial in comparison to the other, complications, advantages and experimental comparisons must be considered. 

Chemotherapy is largely dependent upon patient and cancer type. Chemotherapeutic drugs possess the ability to infiltrate the bloodstream and target metastasized cancer cells. In early cancer stages, while surgery is more prominent, chemotherapy can be used both after and before surgical procedures. Chemotherapy used prior to surgical removal of a tumour is used to minimise the size of the tumour.  If cancer cells are still present in minimal amounts post procedure, chemotherapy is used to eradicate remaining cancerous cells (Cancer Research UK, 2023). A patient with a metastatic tumour of the lung, after extensive chemotherapy, may have an extended lifespan of almost a year, dependent on individual patient factors. Palliative chemotherapy prevents the division of cancer cells, shrinking tumours to allow for an alleviation of pressure of surrounding tissues and organs. Eventually, a duration of response from cancerous cells results in resumed uncontrolled division (Weissman, 2023).

Chemotherapeutic drugs are unable to differentiate between healthy cells and cancer cells, leading to the destruction of functional cells. As a result, immediate side effects such as sickness, hair loss, tiredness and such can occur, though are easily curable through dosage adjustments (Patient Care at NYU Langone Health, 2024). Late side effects appearing years or months after treatment are commonly long term consisting of heart problems, kidney failure, risk of secondary cancer, nerve damage, lung tissue damage or infertility. Chemotherapy is so heavily reliant upon patient and cancer type that numerous studies have been contributed to determining the relationship between dosage, combination of chemotherapeutic drugs or productivity of radiotherapy/other treatments to the type of cancer present (Mayo Clinic, 2024). 

Radiation as a treatment for NSCLC is often commended for its accuracy in targeted destruction. Radiation eliminates cancerous cells and any surrounding functional cells that possess rapid regenerative ability. Radiation results in numerous side effects dependent upon location of treatment. Though, most side effects are not initially prevalent after treatment has commenced. The area of radiation exposure often develops irritation, functionality disruptions, and extensive soreness (Mayo Clinic, 2023). Long term side effects are significantly less predictable in relation to the time of its appearance. A common permanent side effect of radiotherapy is anaemia. Anaemia, a result of lack of oxygen from blood cells, can contribute to tiredness and can oftentimes affect energy/job performance (NHS, 2023).

A randomised trial develops the idea that radiotherapy in early developed NSCLC for patients who are not eligible for surgery is equally effective to typical medical surgeries that are most commonly used (Stereotactic Body Radiotherapy Versus Sublobar Resection for High-Risk Patients with Early Stage Non-Small Lung Cancer). A similar study studied the effect of the same type of radiotherapy on lung cancer and sarcomas specifically (Stereotactic Radiation Therapy for Pediatric Sarcomas). The results conclusively demonstrated radiotherapy’s progressive effectiveness due to its ability to accurately target a tumour without damaging surrounding healthy tissue/cells, especially in comparison to surgical treatments used (Laack, 2019).

Surgery is the most prominent and effective treatment for early detected NSCLC, though it is almost always accompanied by another treatment type (Dadjzie, 2024). Surgery is used to remove a tumour prior to metastasis (Dadjzie, 2024). A large conflict faced with surgery is its increasingly selective availability. In order for a patient to be eligible for surgery, they must be fit with healthy organs/tissues and the tumour must be small at an early stage for successful extraction (American Cancer Society, 2024). Even when a patient fulfils such requirements, side effects from surgical complications, in particular cases, outweigh the consequences of not performing the surgery at all; therefore preventing patients from surgical recommendations. In NSCLC, side effects resulting from the removal of parts of the lung, lung tissue, and lymph nodes can include decreased lung capacity, periodic bursts of pain or shortness of breath (American Lung Association, 2024). Possible surgical complications can result in blood clots, anaesthetic reaction, internal/external bleeding, and, in few cases, death during operation (American Cancer Society, 2019). Despite these numerous obstacles, surgical removal is almost always the most guaranteed treatment for early stages of NSCLC. 

In contrast to eliminating a tumour, gene therapy addresses the factor responsible for uncontrolled cell division, decreasing harm to surrounding cells and risk of reappearance (Cleveland Clinic, 2023). When such treatment is functional, sickness or low blood pressure may occur, though no fatal side effects have been recorded. The most prominent fault in this technique is its low rate of success. Due to the novelty of this treatment, genetic alteration does not consistently occur. Very few genetic therapies have successfully adjusted cancerous cells to be functional. When not functional, gene therapy can result in fatal, unpredictable side effects, largely due to the utilisation of foreign materials triggering immune responses which negate further treatment (Dresden, 2021). In addition to this, gene therapy targets and alters the genetic makeup of healthy cells in addition to or instead of cancerous ones. A genetic alteration significant enough could potentially lead to a formation of a secondary cancer. The vector, a virus with a removed infectious agent, can, in some cases, develop infection when injected within the body (Mayo Clinic, 2024).

Only select gene therapies have been approved to be used outside of experimentation. In counter to harmful vectors, clinical trials have begun to test stem cells and liposomes as vectors in contrast to viruses to avoid risking an immune response. As of 2017, it was shown that the restoration of the tumour suppressor gene through gene therapy decreased growth rate and tumour size by 50% (Nagase et al., 2020).

Similar to gene therapy, targeted drugs directly influence the causation for cancer formation rather than the removal of a harmful tumour. The developed drugs used are especially efficient due to their specialisation in programmed function dependent on its target present inside a cancerous cell. A targeted drug prevents cancerous division with minimal harm to outside cells by affecting the factor of mutation (Cleveland Clinic, 2022). Targeted drugs also destroy pathways, preventing growth more significantly than other traditional methods (Cancer Research UK, 2024). Side effects are considerably minimal and easily curable, including issues in blood concentration, liver problems and diarrhoea. After treatment has commenced, through medication, symptoms greatly decline (Cleveland Clinic, 2022). The larger conflict presented is the rate at which targeted drugs can be developed. Their specificity to cell targets regard a decrease in the amount of cancers that can be treated with developed drugs. Only cancers possessing the target for pre-developed and approved targeted drugs are able to be treated. After extensive treatment, the rate at which cells mutate and adapt is great enough to allow them to develop separate division patterns. In addition to this, prior to injection, a biopsy must be taken to test for the target present in cancer cells, regarding numerous other side effects (NCI, 2022).

A large factor contributing to the rate of development in targeted drugs is the price and difficulty of development (Rath, 2024). As a result, numerous experiments utilising stem cells as a vector to avoid immune system detection have been developed. The stem cells derived from a patient’s bone marrow are used to deliver substances and mark cancerous cells for removal (NCI, 2023). A major drawback to this treatment, however, is the extensive cost and ethical concerns associated with stem cell treatment (Harvard Stem Cell Institute, 2024).

Stem cells are derived from the bone marrow of embryos, raising ethical concerns involved in the destruction of life. When making typical targeted drugs, clinical trials example combinations based upon increasing presence of cancer causing receptors such as EGFR (Harvard Stem Cell Institute, 2024). Another method of development is experimenting with chemical compounds and their effect on mutation inhibition in enzymatic pathways contributing to cancer division (Dana Farber Cancer Institute, 2024). 

When taking into consideration the relative extremities of both modern and traditional treatments, a common factor was that traditional treatments, while not as efficient or conclusive as modernised techniques, were more reliably safe and cheaper. The modernised techniques listed provided necessary studies and significant ideas to be developed for future treatment. Though currently, traditional treatments present a more stable, economically efficient and well developed/known form of cancer alleviation.

4.1 Conclusion

NSCLC is a generally less aggressive, not commonly metastatic cancer. More progressive and modern treatments are only typically necessary in crucial, late stages of cancer. In a stationary, benign tumour, a combination of surgery and radio/chemotherapy is sufficient to allow for functionality (NCI, 2024). Taking medical risks using underdeveloped modernised treatments with minimal knowledge or guarantee is completely unnecessary when NSCLC, in most cases, does not require that extent of medical technology. A combination of modern treatments and exposure to radio/chemotherapy could also prove sufficient, but direct reliance upon underdeveloped methods is unwise. 

Each patient and case, however, has variations. The extent of compatibility with traditional methods is not as broad as the selective requirements for modern technology. A patient unfit for surgery or chemotherapy, due to their physique or susceptibility to immune diseases, may have an easier time and more efficient treatment using experimental modern treatment, especially for NSCLC because there are approved targeted drugs for that specific cancer.

While it should always depend on a patient’s comfortability and personal case, a primary factor in the decision in treatment should be the extent at which each treatment is practised and the direct necessity in proportion to the risks.

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