Cancer Treatment from Past to Present

Cancer is recognized as a major health problem worldwide. Research in recent years has played an important role in understanding the causes of cancer and its treatment methods. In this article, we will provide an overview of cancer and information about research conducted in recent years.

According to the 2023 United States Cancer Statistics, cancer-related mortality (the death rate) decreases by %2 each year, while the number of new cases increases by around %1 annually. The reduction in mortality can be attributed to new-generation cancer treatments.

What Is Cancer?

Cancer is a group of diseases caused by uncontrolled and irregular cell division resulting from accumulated genetic changes.

Under normal conditions, cells divide according to a particular program and produce new cells. However, cancer cells do not follow this program and begin to multiply uncontrollably. Over time, these cells can form a tumor , a mass that may be malignant (cancerous) or benign (noncancerous) (see what is cancer: in detail).

The genetic nature of cancer stems from changes in the DNA of cancer cells. DNA is the basic genetic material of cells, and this material is copied whenever a cell divides. Accumulating changes in the DNA of cancer cells can cause cells to stop following their normal division program and multiply uncontrollably. These changes generally do not occur randomly; they may be associated with particular risk factors. For example, smoking, excessive exposure to sunlight, infections with certain viruses, and hereditary predisposition can increase cancer risk and cause changes in the DNA of cancer cells.

Cancer as a Growing Global Problem 

People fear cancer because the disease can cause death if it is not treated appropriately. Cancer itself and its treatments can affect quality of life. The disease and treatment processes can place psychosocial, spiritual, and financial strains on both patients and their relatives. Moreover, the effects of this multifaceted health problem at societal and global levels are an unavoidable reality.

According to the 2020 World Cancer Statistics, global cancer incidence (the number of new cases) was approximately 19.3 million per year, while cancer-related deaths numbered approximately 10 million annually. These statistics show that cancer is a serious health problem worldwide.

The Past and Present of Cancer Treatment

The Birth of Chemotherapy

Modern cancer treatment began with the low blood counts observed in soldiers exposed to mustard gas used in World War 2. However, until 2000, cancer treatment largely focused on identifying drugs that directly killed cancer cells.

Chemotherapy is one of the most commonly used methods of cancer treatment. Cancer survival rates have increased substantially since its discovery. For example, in the 1950s, average survival for breast cancer was %25-30, whereas today this rate is close to %90.

In addition to breast cancer, chemotherapy has proven effective particularly in cancers such as leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, testicular cancer, ovarian cancer (cancer of the female ovaries), kidney cancer, lung cancer, neuroblastoma, rhabdomyosarcoma, and Wilms tumor.

For example, in the 1970s, %20 of leukemia patients were alive five years later, whereas today this figure has reached %70-90. Similarly, five-year survival for Hodgkin lymphoma has increased from %40 to %80. Platinum-based chemotherapies increase patients' treatment response rates. In the 1980s, the use of platinum-based chemotherapy increased survival in testicular cancer from %10 to %80. Today, testicular cancers are almost completely curable, and survival exceeds %90 even in patients with advanced disease. 

Cancer treatment has made significant progress over the years. Although conventional chemotherapy drugs have been used to treat the disease, research in recent years to better understand the characteristics of cancer cells has enabled the development of targeted therapies. These include drugs aimed at particular targets in cancer cells and new treatment methods such as immunotherapy.

Targeted Therapies

Targeted therapies are drugs aimed at particular targets in cancer cells; they are also called smart drugs. By targeting specific proteins or other molecules in cancer cells, these drugs seek to stop their growth and multiplication. Targeted therapies attack cancer cells more specifically while causing less harm to normal cells.

Among the best-known examples of drugs developed for the first targeted cancer treatments are Herceptin, Avastin, Gleevec, and Tarceva. These drugs work by targeting signaling pathways required for cancer cell growth and spread, helping kill cancer cells or stop their growth. They may be more effective when cancer cells have a particular protein or receptor and may therefore be more suitable for certain types of cancer.

For example, in a study of patients with HER2-positive breast cancer, the use of targeted therapy increased 5-year survival rates from %50 to %85.

Immunotherapies

Cancer immunotherapy is a treatment used to help the immune system recognize and destroy cancer cells. The immune system normally protects the body against disease, but cancer cells may evade its detection in various ways, or the immune system may recognize them but be unable to destroy them. Immunotherapy is a method used to make the immune system more effective against cancer cells.

In the 1960s, studies in immunology began to improve understanding of the interaction between immune system cells and cancer cells. Researchers discovered mechanisms that prevented the immune system from destroying cancer cells.

In the 1990s, CTLA-4, a protein found on the surface of cancer cells, was identified as a mechanism preventing immune system cells from interacting with cancer cells. Researchers discovered that antibodies blocking the CTLA-4 protein increased the immune system's response against cancer cells. 

In the 2000s, another protein called PD-1 was discovered. The PD-1 protein was found to be used by cancer cells to suppress the immune system. The use of antibodies blocking the PD-1 protein, which are called immune checkpoint inhibitors , can help immune system cells destroy cancer cells (see James Allison and Tasuku Honjo's 2018 Nobel Prize in Medicine for their cancer immunotherapy studies).

These discoveries made it possible to use immunotherapy in cancer treatment. Today, immunotherapy has become a standard method of cancer treatment and is used for many types of cancer.

Immune checkpoint inhibitors have significantly increased survival rates, particularly in certain cancers such as melanoma, lung cancer, and kidney cancer. However, their effectiveness is more limited in other cancers, such as breast cancer, colorectal cancer, prostate cancer, and pancreatic cancer.

For example, in melanoma, an aggressive skin cancer, the use of immune checkpoint inhibitors has increased 1-year survival to %69-74, 3-year survival to %40-50, and 5-year survival to %34-44. Before immunotherapy was used, 1-year survival in melanoma was generally around %30, 3-year survival was %10-15, and 5-year survival ranged from %5-10. 

In lung cancer, the use of immune checkpoint inhibitors, particularly the PD-1 inhibitor pembrolizumab, is effective in delaying disease progression and substantially increasing survival rates. In kidney cancer, immune checkpoint inhibitors are also effective in delaying progression and increasing survival. In particular, the combination of nivolumab and ipilimumab has increased 2-year survival in metastatic kidney cancer to as much as %64.

Early Diagnosis

Early diagnosis is one of the most important factors in cancer treatment. The earlier cancer is diagnosed, the more successful treatment is. Cancer screenings and the increasing numbers of informed patients and physicians have helped increase early cancer diagnoses. In addition, detecting epigenetic changes specific to cancer cells and cancer-associated proteins could represent a breakthrough in early cancer diagnosis.

Surgical Techniques

Cancer surgery techniques have advanced in recent years, with methods that cause less damage to patients' bodily integrity coming into use. These techniques aim to remove cancerous tissue while preserving healthy tissue.

Radiotherapy

Radiotherapy uses high-energy radiation to kill cancer cells. In recent years, advanced-technology radiotherapy techniques have been developed; modern equipment and delivery methods maximize tumor destruction while minimizing side effects in normal tissue.

Where Do Modern Cancer Drugs Come From?

Modern cancer drugs are discovered through collaboration between the laboratories of the United States National Cancer Institute (NCI), research institutes worldwide, and companies. NCI laboratories conduct tumor screening tests using thousands of plants and marine organisms and investigate approximately 140.000 synthetic chemicals and 80.000 plant extracts and other biological materials for potential antitumor effects. Drug effectiveness is tested in tumor cell cultures and mice, and successful candidates enter clinical trials for use in humans. Drugs approved by national organizations such as the FDA (United States Food and Drug Administration), EMEA (European Medicines Agency), and the Turkish Ministry of Health play an important role in cancer treatment.

Practitioners of alternative medicine argue that natural products provide healing without harming patients and claim that modern drugs do more harm than good. However, modern medicine has questioned these claims, and herbal medicines have been shown to be ineffective in treating cancer. Advances in cancer treatment have come through identifying mechanisms that stimulate uncontrolled cell growth or inhibitory steps that have malfunctioned. Drugs developed against these mechanisms are effective in many types of cancer, and important results are being achieved by individualizing treatment according to cancer subtypes and genetic differences. Ignoring these advances and directing patients toward alternative medicine poses a serious threat to patients' right to life.

In summary;

• Modern cancer drugs consist of a range of medicines targeting the growth, multiplication, or spread of cancer cells. These drugs specifically target cancer cells and have less effect on healthy cells.
• Discovering and developing these drugs is a very long and challenging process. Drug discovery generally begins in the laboratory, where candidate drugs are identified using methods such as screening tests and cell cultures.
• Animal models may then be used to develop drugs specific to a particular cancer type. These models are designed to simulate how cancer cells behave in humans. At this stage, drug safety and effectiveness are tested.
• Before a candidate drug can be tested in humans, it enters the clinical trial stage. Clinical studies provide information about the drug's safety, effectiveness, dosage, and side effects. A drug is generally tested in three different phases, each involving a larger group of patients.
• In the final stage, the drug is approved by the relevant agencies around the world and becomes available for marketing. This approval process includes strict regulations governing the drug's manufacture, distribution, and sale.

Today, modern cancer drugs are generally produced using biotechnological methods. These methods include techniques such as genetic engineering, protein synthesis, and cell cultures.

Drug manufacturers also produce specific medicines, such as drugs that block the production of particular proteins in cancer cells or antibodies targeting proteins produced by cancer cells. Because these drugs specifically target cancer cells, they may cause fewer side effects.

In conclusion, discovering and producing modern cancer drugs is a very long and challenging process. However, these drugs play an important role in cancer treatment and help increase survival rates.

Why Have All Cancers Still Not Been Completely Cured?

There are many reasons why cancers cannot be completely cured. The most important are as follows:

1. Cancers have different types and subtypes: Cancers can occur in different types and subtypes, and their treatments may differ. Therefore, treatment for each cancer is tailored to the individual.

2. Differences between the cells of cancers: Cancer cells may have characteristics different from normal cells, meaning the control mechanisms present in normal cells may not work in cancer cells. Treatments must therefore be specially designed to kill cancer cells without harming normal cells.

3. Cancer's ability to spread: Cancer cells may be able to spread to other parts of the body and subsequently form new tumors there. Cancer treatment must therefore address the whole body rather than focus only on one area, to reduce the risk of tumor spread.

4. Cells resistant to treatments: Cancer cells can develop resistance to treatment. This may render the drugs used in cancer treatment ineffective. Consequently, treating the disease may require different drugs and alternative treatment methods such as radiotherapy and immunotherapy.

5. Difficulty with early diagnosis: Some cancers may be difficult to diagnose in their early stages. Early diagnosis plays a critical role in treatment success. However, cancers can often develop for a long time before symptoms become apparent. Regular screening tests are therefore important for early diagnosis.

Considering all these reasons, cancer treatment is a difficult process, and an inability to achieve a complete cure is quite common. Nevertheless, ongoing advances in cancer treatment mean that many cancers can now be treated more successfully, and new treatment options are expected to be developed in the future.

Is Using the Right Drugs Alone Enough for Successful Treatment?

Medical treatment for patients with cancer includes communication and support involving the patient, their family, and their social circle, as well as administering the right drug at the right time and dose. Cancer treatment therefore requires a comprehensive approach that includes patient care, education, and psychological and physical rehabilitation alongside medical treatment.

Patients' strength to hold on to life is directly proportional to their trust in their physician and treatment. All cancer treatment organizations should therefore aim to consider the patient, their family, and their social circle as a whole and provide the maximum benefit to the patient.

Cancer treatment should address different areas, such as physical rehabilitation, sexual rehabilitation, and psychological support, and maximize patients' quality of life during and after treatment. By increasing adherence to treatment and commitment to life, this approach can help achieve more successful outcomes in the fight against cancer.