Lung Cancer Therapy: Overview of Treatment Methods

Lung cancer – referred to as ‘lung carcinoma’ or ‘bronchial carcinoma’ in specialist jargon – describes malignant tumors that develop from the lung tissue. It usually develops from the cells of the alveoli or bronchial cells. There are several risk factors for the development of lung cancer, including age, gender, ethnicity, genetic predisposition, smoking (tobacco and cannabis), environmental pollution, infections, inflammation and Chronic Obstructive Pulmonary Disease (COPD). Tobacco smoking is the most important factor here: it is responsible for more than two thirds of deaths and has been proven to be the cause of 80% of illnesses.

The latest data shows that more than 2.2 million people worldwide were diagnosed with lung cancer in 2020 and almost 1.8 million deaths were recorded. This makes lung cancer the leading cause of cancer-related deaths worldwide. Its poor prognosis is due to the fact that this cancer type is only detected at an early stage in 15% of cases. In most patients, the cancer is already at an advanced stage by the time of diagnosis.

However, thanks to the rapid development of diagnosis and treatment methods, the 5-year survival rate of lung cancer patients has improved significantly in recent years. It has risen from around 11.5% in the mid-1970s to around 20.5% in the 2010s. This is also due to the introduction of new treatment methods such as immunotherapy and personalized lung cancer therapy.

Lung cancer treatment and the prognosis for those affected depends primarily on the form of the disease (non-small cell lung cancer or small cell lung cancer) and the stage of the disease. A distinction is made between the following types of lung cancer:

Non-Small Cell Lung Cancer (NSCLC): This variant accounts for the majority of all lung cancers. The three most common forms of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Locally effective therapies (e.g. surgery, radiotherapy) and systemically effective treatment methods (e.g. chemotherapy, targeted therapy, immunotherapy) are available. These are often used in combination (e.g. radiotherapy and chemotherapy).
Small Cell Lung Cancer (SCLC): This variant is extremely aggressive. Lung carcinoma grows rapidly. It also spreads to other organs outside the lungs at an early stage. The treatment options depend on the stage of the disease, the patient's age, state of health and previous illnesses. Due to the rapid growth and early formation of metastases, the prognosis for small cell lung carcinoma is worse than for the non-small cell variant. However, clinical studies conducted as part of oncology research are constantly providing new findings. These are also being used to improve lung cancer treatment in this area.

The treatment options for non-small cell lung cancer (NSCLC) mainly depend on factors such as tumor grade, size and location of the tumor, lymph node status, the patient's general health and lung function.

Stage II: The tumor is 4-5 cm in size (IIA) and there is neither lymph node involvement nor metastases. In stage IIB, the tumor is up to 7 cm in size or has grown into the chest wall/pericardium or there is an additional tumor in the same lobe of the lung. A smaller tumor is also classified as stage IIB if the surrounding lymph nodes are involved but there are no distant metastases. In stage II, after surgical removal of the cancer, concomitant chemotherapy, radiotherapy and immunotherapy can be carried out.

Stage IIIA: This stage includes many forms, from very large tumors without lymph node involvement to relatively small tumors that have already formed lymph node metastases below the tracheal bifurcation. There are no distant metastases. A combination of chemotherapy, radiotherapy and/or surgery together with immunotherapy can be used as initial treatment for stage IIIA. For patients whose cancer cells have specific mutations in the EGFR gene, additional targeted therapy with a specialized drug may also be considered.

According to World Cancer Research Fund International, lung cancer is the most common tumor disease worldwide.

In the UK, it is the second most common cancer type in males and females alike with about 49,000 new cases a year. It is also the most common cause of cancer death with about 21% of all cancer deaths. The risk of developing the disease increases with age: in men, the age group of 80 to 84-year-olds is particularly affected, while women over 75 years of age have a particularly high risk of developing the disease. In the US, lung cancer is also the second most common cancer type in both men and women with about 235,000 cases a year. It is the leading cause of cancer death in the US and mainly people aged 70 and older are affected.

The earlier lung cancer is detected, the better the chances of recovery. However, bronchial carcinomas rarely produce specific symptoms in the early stages. Those affected often only experience non-specific signs such as coughing or slight shortness of breath, which can easily be mistaken for other, less serious illnesses. The typical symptoms only appear at an advanced stage.

In high-risk groups such as smokers and people over the age of 50, an annual lung cancer screening can be carried out using low-dose computed tomography (LDCT) to detect any existing lung cancer so that treatment can be initiated as early as possible. LDCT effectively detects small tumors. However, there are challenges with this procedure in terms of sensitivity and specificity. This means that there are both false positive results (leading to unnecessary interventions) and false negative results (where the cancer is not detected).

In parallel, intensive research is being carried out to develop biomarkers that could enable earlier and more accurate diagnoses. But so far, only a few of these biomarkers have demonstrated sufficient sensitivity and specificity to be practically used in diagnostics.

Surgery

For non-small cell lung cancer (NSCLC), surgical removal of the tumor is the gold standard, provided the tumor is operable and the patient's state of health permits surgical intervention. Surgery is mainly used to treat non-small cell lung cancer in stages 0 to II. Depending on the size and location of the tumor and the capacity of the lung, a lung lobe, a lung segment or the entire lung is removed. Traditionally, this was carried out using an open thoracotomy. Thanks to technological advances, video-assisted thoracic surgery (VATS) is currently used in particular, as it has fewer negative postoperative consequences for patients compared to thoracotomy. The latest technique for surgical tumor removal in NSCLC is robot-assisted thoracic surgery (RATS), which offers greater accuracy thanks to the precise movements of the robotic arms.

Radiotherapy

Radiotherapy is an important method of treating lung cancer and can be used at any stage of the disease as a complementary (adjuvant) or preparatory (neoadjuvant) therapy. The tumor is damaged using high-energy radiation in order to slow down or stop the growth of cancer cells. Radiotherapy can be used on its own or in combination with other treatment methods, such as surgery, chemotherapy, immunotherapy, targeted, nanoparticle or CRISPR therapy. There are three types of radiotherapy: conventional radiotherapy with low radiation doses and longer treatment duration, SBRT with high radiation doses and short treatment duration or intensity-modulated radiotherapy with adjusted doses and longer treatment duration. SBRT is more complex, but has proven to be more beneficial in studies.

Chemotherapy

During chemotherapy, patients are treated with special drugs known as “cytostatics”, typically by infusion. In non-small cell lung cancer (NSCLC), chemotherapy aims to slow tumor growth, reduce the tumor mass and alleviate symptoms, especially in advanced stages. In small cell lung cancer (SCLC), chemotherapy is used to control the rapid growth and spread of cancer cells and prolong survival, as this cancer is usually more aggressive and usually metastasized at diagnosis. Chemotherapy can be combined with other treatments such as radiotherapy, immunotherapy, targeted therapy and surgery. Before surgery, chemotherapy is used to shrink the tumor and facilitate its removal. After surgery, it has been shown to be effective in reducing the mortality rate in stage IB patients.

Immunotherapy

Immunotherapy is a new and advanced method of treating lung cancer that specifically supports the patient's immune system. Cancer cells have developed numerous strategies to avoid programmed cell death (apoptosis) and destruction by the immune system. Targeted strengthening of the immune system through immunological therapies is therefore necessary. There are various approaches to immunotherapy. The two main strategies focus on so-called “CD8+ T cells” and on factors that influence their function. These include, for example, cytokines — small proteins that control communication between the cells of the immune system. Immunotherapy is generally used in advanced lung cancer, but can also be used in combination with other therapies such as chemotherapy or radiotherapy to increase their effectiveness.

In recent years, the treatment of non-small cell lung cancer has evolved from conventional surgery, chemotherapy and radiotherapy towards tailored and minimally invasive approaches. The use of personalized therapies for the treatment of lung cancer has surpassed the expected efficacy. At the same time, targeted therapies and holistic medicine have improved the tolerability of lung cancer treatment for patients by reducing the incidence of serious adverse side effects.

Today, the diagnosis of lung cancer is more often based on immunochemical tests than on visual examination of the tissue under a microscope. Biomarkers play a crucial role in this, especially in cases of uncertain diagnosis. With the ongoing development of next-generation sequencing, genetic screening for lung cancer is also being used more and more frequently. Researchers have discovered specific mutations and gene changes that influence the development of lung cancer.

These findings have made it possible to develop specific therapies that precisely target these genetic changes — the basis for personalized and targeted therapy for lung cancer.

Personalized cancer treatment is an important and groundbreaking new method in medicine. The key feature of this treatment option is that it is tailored to the individual patient based on the genetic, molecular and cellular characteristics of the tumor. These can be identified using special blood tests and treated using personalized therapy. This aims to maximize the success of treatment and minimize the burden on the affected patients.

Compared to conventional therapies, which often have undesired effects, personalized therapy takes the patient’s cancer cells’ behavior into consideration, therefore more appropriate protocols are selected. This approach enables precise treatment of lung cancer and reduces the number of ineffective therapies.

RGCC International is a global laboratory network made up of multidisciplinary teams of researchers. They combine pioneering research with cutting-edge technology to develop targeted cancer therapies and continuously improve patient outcomes. The consideration of biomarkers is crucial to enable individually tailored therapy. A biomarker test can be performed through a blood analysis, for example, using RGCC's versatile cancer blood tests. Through these specialized blood tests, various tumor characteristics can be identified and personalized treatment can then be initiated. These treatments are specifically designed to block the signaling pathways of cancer cells while stimulating the body's immune system and alleviating symptoms.

The following RGGC cancer treatments are generally suitable for the treatment of lung cancer, although the method can only be implemented in conjunction with a RGCC test and after consultation with specialized physicians:

Q-REstrain

Q-REstrain consists of microRNA molecules with the ability to regulate the gene expression of a specific target. The short dsRNAs (double-stranded RNAs) are derived by cleavage of long dsRNA from Dicer and can be microRNAs (miRNAs). miRNAs then assemble with RNA-induced silencing complex (RISC) and cause gene silencing. RNAi has been used in the therapy of different diseases including cancer, viral infections, respiratory diseases, etc. Targeting of specific proteins, through degradation of their mRNA, is very common in cancer treatment of different types of cancer or other infections.
Q-REstrain contains microRNAs isolated by the patient’s sample, leading to the degradation of specific mRNA molecules, which are overexpressed in this specific sample, thus regulating the expression. Q-REstrain is for autologous use only and is provided through the RGCC network.

Clavic-Q-RE

Clavic-Q-RE is an adoptive cell therapy aiming to generate a robust anti-tumor immune response. Clavi-Q-RE contains different cell populations, isolated by the patient’s sample. They include monocytes, natural killer cells, as well as dendritic cells that are already activated in vivo against tumor antigens, which are expressed on cancer samples, cytotoxic T lymphocytes, and plasma cells that have been already differentiated in vivo against tumor antigens. Clavic-Q-RE is for autologous use only and is provided through the RGCC network.

Vaccine Prep (ATA)

Vaccine Prep (ATA) is a new type of immunotherapy that activates or strengthens specific immune cells. The body's own cells are specifically designed to recognize and destroy cancer cells. We use the cellular fragments of dying tumor cells (CTCs). These include organelles, mitochondria, cell membranes and cellular RNA and DNA. In our laboratory, we stimulate the development of dendritic cells and thus promote tumor antigen therapy.

Dendritic Cell Therapy

The aim of dendritic cell therapy is to activate or strengthen the immune system. In immunotherapy, specific immune cells are used to target cancer cells. The therapy method uses so-called dendritic cells, which can recognize specific antigens on the surface of cancer cells. Thanks to improved tumor defense and a reduction in systemic side effects, the therapy is considered a promising treatment approach.

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The researchers at RGCC are dedicated to addressing unmet medical needs and advancing more precise cancer therapies every day. With our chemosensitivity tests and personalized therapies, we want to support doctors and patients in making the diagnosis and therapy of lung cancer and other forms of cancer, such as prostate cancer, colorectal cancer or breast cancer, more effective and minimizing possible side effects.

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