By Manel Esteller, doctor. Josep Carreras Leukemia Research Institute.
Some of the latest drug and cell treatments to treat tumors are already here and used in our hospitals.
You already know that the best disease is the one that does not appear. That cancer prevention is better than its treatment. And that an early detection of a premalignant lesion or a small tumor and its removal by surgery surpasses all the drugs that we can administer. But unfortunately, many times the oncological pathology is diagnosed when the removal by the scalpel is not enough or is physically impossible at that point in time. Therefore, classical chemotherapy and that directed against specific targets of the transformed cell continues to be an essential tool to cure the disease. There is a trend to move from multi-drug therapy regimens to kill any proliferating cells, which for example have changed the prognosis of testicular cancer for the better, to more targeted and generally less toxic treatments. But today I would like to talk specifically about some of the latest drug and cell therapies to treat cancer, many of them new that are already here and are being used in our hospitals.
An example of recently introduced drugs consists of those compounds that inhibit specific components of the molecular machinery that the tumor cell needs to divide excessively. This is the case of the so-called cyclin inhibitors. Every cell lives in a cycle of growth, rest, division, and death. We can imagine it as the wheel of a car, spinning at full speed in a Ferrari and spinning more slowly in a horse-drawn carriage. The speed of these turns depends on proteins called cyclins and in recent times blockers of them have been obtained. Its main application is being in certain subtypes of breast cancer, where in addition to providing a clinical benefit, they are usually well tolerated by patients. In addition, for these patients in this group of breast tumors there was no drug associated with it and now these women are no longer ‘orphans’ in relation to their therapy. Another more recent example is the RAS oncogene. This was the first gene shown to be mutated in cancer. All this happened in the early 80s when the Naranjito thing, more or less. Well, it has taken about 40 years, but we already have the first drugs directed against this genetic alteration of this transforming gene. Its first application will be in patients with lung cancer, a pathological entity that has also recently benefited from immunotherapy.
Speaking of using our defenses against cancer, in addition to drugs we can use “cells that eat other cells.” The idea of these approaches is to extract cells from the immune system, activate them in the laboratory and show them a target of the tumor against which they want to fight. They are the cells called CAR-T, TCR or ‘natural killers’. Those used clinically are currently the first, having meant a paradigm shift in irrecoverable cases of leukemia, lymphoma and other oncological pathologies of the blood. One of the problems is that they are currently very expensive therapies, but it is expected in the coming months, a couple of years, that their price will be lowered by automating their manufacture. There is another cell therapy called TIL: they are our T lymphocytes that are already attacking the tumor that we extract and concentrate to give them back to the patient. Step by step, cell by cell for healing.
Finally, point out the growing interest and hope for the development of vaccines against cancer. Do not think that they are the same as the triple viral or covid-19 that are general for the population, but here they are personal, specific to each individual. One of the first most promising studies in this area has been carried out in melanoma: using proteins expressed by this tumor in patients, the vaccine is made, so that when the melanoma shows its face again (relapse or recurrence), our body is prepared to receive it as it deserves. We are in this field at its dawn, but great advances are expected in it.
New drugs, new hopes. We are still in the game of cat and mouse. The tumor hides itself, changes its appearance to go unnoticed for one drug, but shows weakness for another. And thanks to research we continue to save time for many patients, also in quality of life. But the road is still long and it is sometimes difficult to discern where on the horizon the sea ends and the sky begins.