A New Era in Cancer Treatment
Cancer is a genomic disease state that can originate from almost any organ and tissue of the body, is characterized by uncontrolled cell proliferation, can spread to other parts of the body, and can sometimes be hereditary. In developed countries and in many developing countries, including Turkey, it is—together with heart disease—the most important cause of disease-related deaths. Cancer is heterogeneous and is not a single disease; it is a very broad group of diseases. Until recently, these differences were addressed through an organ-based classification of cancer. Organ-based definition, which might also be called address-based (for example, lung cancer, breast cancer, colon cancer, and so on), was built on the logic that all cancers originating from the addressed organ are similar. In the light of new studies, however, it has been seen that cancers originating from the same organ can be very different, while cancers of different organs can display very similar characteristics. Essentially, what matters is not which organ the cancer originates from, but how it develops and the changing biology of the cell. For this reason, approaches in which cancer is evaluated on a molecular basis and individually are coming to the fore. Articles recently published in "Nature" and "CA: A Cancer Journal for Clinicians"—among the most important journals in the world of science—provide guidance on why we should move from organ-based approaches to molecular-based approaches, and on how the genomic test results that make this possible should be evaluated in clinical cancer practice.
Molecular-Based Evaluation in Cancer
The article in Nature sheds light on the limitations of organ-based classifications and proposes a shift to a molecular-based classification. Such a change, by revealing the true complexity of cancer, will pave the way for more effective treatments and better patient outcomes. The organ-based system often disregards the complex biological differences of distinct tumors, and can lead to misdiagnoses, ineffective treatments, and to patients who could benefit from personalized treatment missing out on these opportunities. For example, cancers that arise in different organs may harbor quite similar genetic mutations, which renders the organ-based label misleading and hinders the development of targeted therapies. Moreover, since tumors in the same organ can display very different behaviors and treatment responses, this system can mask critically important information. The molecular approach, on the other hand, by investigating the genetic and other molecular features underlying each tumor, offers a deeper insight into its unique biology and sensitivities. This allows for a more precise diagnosis, personalized treatment strategies, and the development of new treatments that specifically target the unique molecular structure of the tumor.
The article also shares some recommendations to enable and facilitate this transition. For example, cancer centers and university hospitals can establish organ-independent teams focused on interpreting molecular analyses. The medical education curriculum should comprehensively cover the molecular foundations of cancer development and the design of treatment according to the genetic alterations of cancer. Improving access to molecular tests and updating their methodology and guidelines to be prepared in line with the new era are also among the steps that need to be taken. Regulatory bodies, scientific communities and insurance companies should take on responsibility as natural components of the process.
One of the important points in the article is that, because drugs targeting a specific biological mechanism are approved on an organ-specific basis, tumors in other organs that carry the same mechanism cannot benefit from these treatments. While the drug olaparib was approved in BRCA-mutant tumors in 2014, it was approved in BRCA-mutant breast cancers in 2018 and in prostate cancer in 2020. After 2014, thousands of breast and prostate cancer patients were unable to benefit from this treatment. Had the approval in 2014 been granted not on an organ-specific basis but solely on the basis of the BRCA defect, thousands of patients would have been able to benefit from these treatments. However, scientific transformations take time. If there is no safety concern, drugs targeting specific biological mechanisms defined in cancers should be approved not on an organ-specific but on a mechanism-specific basis.
If There Is a Target, It Applies to All Cancers
The second article was written to provide a practical guide on how genomic information should be interpreted and integrated into routine cancer care. Although genomic tests can lead to better outcomes by providing information about cancer risk, prognosis and therapy selection, they are not used sufficiently in routine cancer practice. Practical guidelines on how genomic information should be interpreted in the clinical setting and integrated into the treatment process, aimed at clinicians who are not experts in cancer genomics, are currently limited. Therefore, one of the difficulties encountered—and perhaps the most important—is the lack of knowledge and understanding among healthcare providers (in the case of cancer, medical oncologists) regarding how to interpret the results of genetic tests. The fact that access to genomic tests and, in cases where a therapeutic target has been identified, to innovative treatment options, is still not at the desired level, is perhaps one of the most important factors giving rise to this problem. Since these next-generation technologies will become increasingly accessible, the construction of sustainable healthcare and reimbursement systems should begin now. For this reason, by getting to the root of the problem, the principle of precision oncology will need to be integrated into medical education. At the same time, in order to provide healthcare covering the entire spectrum of precision oncology, it is inevitable that molecular pathologists, molecular biologists, scientists, bioinformaticians and technical staff also be subject to an appropriate training curriculum and included in the process.
The most important point noted in both articles is the lack of genetics training among oncology physicians engaged in clinical practice and the need to bring the education curriculum in line with the new era. However, due to the rapid change in the science of genetics and the increasing information load, it is not possible to complete the genetics education of existing oncology physicians. Personalized cancer treatments also contain information far too complex to be carried out with simple guidelines. At the very least, the genetic data specific to each patient must be processed, the changing biology of that patient's cancer must be analyzed, and cancer treatment must be planned accordingly. To carry out this approach, oncologists actively working in the clinic have neither sufficient time, nor sufficient knowledge, nor sufficient experience. For this reason, the most practical and rational solution is the integration into the clinic of scientists who know genetics, who can analyze biological behaviors and who know bioinformatics—that is, molecular biologists and geneticists, bioinformaticians and the like who are experienced in cancer. In this way, it becomes possible to increase the transition between research and clinical practice, to perform genomic profiling analyses more efficiently and accurately, to address the shortage of genuine experts in the field of molecular oncology, to analyze and make sense of each cancer in a personalized way, and to successfully design and apply personalized treatment approaches. The further acceleration and broader spread of this process will be a natural result of new scientific developments. With the addition of different types of data as well, it can be expected that treatment success will rise and survival rates will increase proportionally. In short, the future in the treatment of cancer—and potentially of all diseases—lies in personalized molecular approaches. For this reason, it is essential that the changes and planning that will make this possible be carried out in the education of related fields such as oncology and biology, that the participation of scientists in clinical practice be increased, and that treatment processes be guided by multidisciplinary boards.
An even more important point is that new job opportunities will emerge for our scientists who possess significant knowledge and experience in the field of molecular biology and genetics, and our country could also become a center of attraction in this field. It will not only be a reason for our own scientists to return to our country, but we will rise to a position that other scientists too will want to come to. At this point, training specific to this field should be organized to raise CLINICAL CANCER BIOLOGISTS. In every center where cancer treatment is provided, environments should be created in which molecular and genetic tests are evaluated and presented to oncologists, and in which treatment decisions are made by evaluating all the data.
In the new era, cancer treatment will be a process in which scientists and clinicians work together to pave the way for more successful treatments.
The era of organ-specific, same chemotherapy for every patient has come to an end.
The era of personalized, tumor-agnostic, molecular and biology-based cancer treatment has begun.