The concept of agnostic tumor is a further step towards precision oncology, with therapies aimed directly at the genetic alterations that cause the tumor, regardless of its location.
This year, medicine has given us many lessons. One of them is the importance of a good diagnosis. Screening tests and different ways to detect a disease are essential in preventing many diseases, but also
when deciding what will be the best treatment for a patient. It happens with special importance in the case of cancer.
Although cancer has in many cases become one curable disease and in others, can prevent (According to WHO, 30% of cancer deaths could be prevented by avoiding risk factors such as smoking, poor eating habits or sedentary lifestyle), is a disease that continues to raise many unknowns about their behavior.
Decades of research have paved the way for one of the latest aspects of treatments, the agnostic approach to cancer. The most advanced DNA sequencing techniques have made one possible deeper genetic study of tumors, Encouraging the discovery of genetic alterations (or biomarkers) responsible for certain types of cancer. They are the last piece of information available and they allow direct treatments taking into account the genetic characteristics of the tumor, Beyond its location and stadium. It is what is known as
precision medicine.
For Dr. Rosario García Campelo, head of the Oncology Service at the CHUAC and head of the Oncology Group at the INIBIC research center in A Coruña, the main innovation of recent years has undoubtedly been the “Genomic characterization of cancer. This dissection we have done of the different tumors, there is no longer a single lung cancer, but
we know several subgroups based on certain genetic alterations which have allowed for a personalized approach “.
Lung cancer is the best example for understanding the concept of precision medicine, according to Dr. Garcia. “We started in 2004 with a real biomarker revolution with the discovery of EGFR gene mutations and since then the list has not stopped growing. “Some, like the NTRK gene, exemplify it perfectly:” it has been described in very rare tumors as pediatric tumors and very common tumors as lung cancer. ” There are currently more than 700 biomarkers under study.
- Dra. Rosario García
- Dra. Lara Pijuán
- Dra. Lara Pijuán
Lung cancer is the second most common in the world, with more than 2 million cases each year. In Spain they are diagnosed near 30,000 new cases each year, According to the Spanish Society of Medical Oncology. It is, moreover, the most deadly type of cancer, being responsible for 20% of all cancer deaths. But, on the other hand, it is also one of the diseases in which the most progress has been made in recent years, and great progress has been made in reducing mortality, diagnostic techniques and new treatments.
There are two classifications for lung cancer: small cell (microcytic) and large cell (non-microcytic). the first it represents only 15% of cases, however, it is the most aggressive and is usually detected in already advanced stages of the disease, with metastasis. Research and genetic knowledge of this type of tumor has made it possible to obtain new drugs and therapies and “It has radically changed the way we understand cancer and especially the way we treat our patients.”, Points out the oncologist.
Precision medicine
The success of so-called precision medicine, which allows specialists to know what treatments will work in the patient based on the genetic dissection of their disease, Depends greatly on the diagnosis. “How we diagnose cancer now is nothing like what we did ten years ago. Depending on the ‘name’ we give to a tumor, we need to add genetic studies and look for molecular alterations,” explains Dr. Lara Pijuan Andújar. , pathologist at the Hospital de la Mar, in Barcelona.
Molecular alterations are what define the concept of agnostic tumor: genetic alterations that are responsible for generating the disease, but that
“They can be present in different organs and can be treated homogeneously”, Determined by Dr. Garcia. That is, with therapies aimed exclusively at these biomarkers, in cancer cells, without affecting any other. That is why it is so important now give cancer first and last names, Says Dr. Pijuán: “It’s not the same to tell a patient who has squamous cell carcinoma that he has adenocarcinoma.”
A good diagnosis, better treatment
It is estimated that around one 30% of lung cancer patients could benefit from these targeted therapiesBut for these treatments to reach everyone, access to the best diagnostic tests is vital. Dr. Pijuán believes that “it is something that needs to be done at the national level, it is not possible for a patient, to be from one place or another, to receive a different diagnosis “. A claim made by the pathology services because “if we are well served, the patient will always have a better treatment.”
The search for these genetic alterations has improved significantly in recent years, thanks to the mass sequencing technique (Next generation sequencing or NGS), which allows “studying many genes in the tumor, and not just those we already know. So we are adding new information, new genes are appearing that need to be studied to see which drug can go against it.” In the laboratories of the Hospital de la Mar, this technology allows pathologists work with panels of between 50 and 200 genes simultaneously.
Taken together, technological advances in diagnostic testing and targeted therapies have completely changed the approach to the most aggressive type of lung cancer. Besides, the results of the new treatments improve those obtained with conventional treatments such as chemotherapy and surgery, With the benefit for patients that “may have some occasional side effects, however it’s not going to attack like chemotherapy “, Points out the pathologist.
The three pillars that now support cancer treatments would be the chemotherapy, targeted therapies and immunotherapy. Immunotherapy treatments are already a reality in lung, bladder, kidney or melanoma cancers, paving the way for their arrival in other types of cancer, such as neck cancer. Immunotherapy works by modifying and modulating the immune system to “Let the individual’s system be responsible for detecting the tumor cell and removing it”, Developed by Dr. Garcia. Specialists talk about one
“A real therapeutic revolution”, Backed by more and more research. Like immunotherapy, the agnostic approach to cancer needs more and better research to continue advances.
New therapies change the direction of clinical trials
The agnostic approach to cancer has also changed the design of clinical trials. Research that traditionally focuses on testing the effectiveness of cancer treatment according to its location. Now, however, with the identification of molecular alterations and the development of targeted therapies, another type of study has begun to be developed, the basket or umbrella trials, In which molecular alteration is prioritized.
Umbrella essays are those that study different drugs in various alterations which occur at a given location: for example, several patients with lung cancer but who have different genetic alterations. Basket trials, on the other hand, evaluate the efficacy of a drug for a single alteration, Regardless of location. That is, different tumors that share the same biomarker.
The emergence of these new clinical trials has opened the door to that more patients have the opportunity to access agnostic therapies. They are also of special importance for the study of rare cancers or unusual alterations. Organizations such as the FDA in the United States and the EMA in Europe consider basketball studies as acceptable methods for authorizing these treatments and so on.
continue to investigate the effectiveness of targeted therapies.
Neither cancer nor other diseases have stopped due to the pandemic, despite a 20% fewer diagnoses this year, According to SEOM, but the availability of new treatments, “immunotherapy or precision medicine, have helped us a lot to adapt the treatments of our patients. To eliminate hospital attendance, oral treatments have allowed us to have the medication sent home and to do checks using telemedicine. ”