Cancer: what are agnostic tumors and what is their impact on treatments

Agnostic tumors, precision or personalized medicine.

Those are the terms that are used today to talk about cancer and the new possibilities of treatment.

With agnostic tumors we refer to those in which a

is identified that makes it possible to treat them

.

It implies a

: the focus is no longer on the organ (lung, colon or breast);

Now the key is to detect possible mutations or other types of molecular characteristics in order to

.

Matias Chacón, head of Oncology at the Alexander Fleming Institute and former president of the Argentine Society of Clinical Oncology, explains that we came from a

and did not take into account that there could be common alterations to different tumors that could be addressed with certain drugs.

According to Chacón, we are talking about very recent technologies that exploded with the knowledge, first, of the

and then of

.

“The complete sequencing of cancer, with all its genetic alterations, was published in the scientific journal

in February 2021”, highlights the specialist who clarifies that “further research is needed”.

A colorectal cancer organoid, with the cells responsible for the metastasis marked in red.

Photo: IRB Barcelona

Immunotherapy for tumors that fail to repair DNA errors

The first agnostic therapy, he details, was approved in 2017. “It is an immunotherapy called pembrolizumab for tumors that

.

That is the

and it usually occurs in cases of colon and endometrial cancer”, he specifies.

And he says that this biomarker can be searched for from

or by

such as identifying certain proteins in biopsied tissue.

Treatment for NTRK gene fusions

"The next approval had to do with the presence of

, present in 0.28% of tumors and usually detected in juvenile sarcomas and thyroid tumors," Chacón points out.

Although it is infrequent, he assures that what is relevant is that if it appears it is like

"The drugs used in this case are

, which were only authorized in Argentina this year," he adds.

Blocking an alteration in the BRAF gene

Another of the agnostic therapies available has to do with the identification of

and the appearance of drugs that can block the product of this genetic variation.

It was detected years ago in cases of melanoma and now this mutation is being found in other tumors such as colon tumors.

On this last alteration (that of the BRAF gene), the Pfizer laboratory presented a new treatment for

.

The new drug is a targeted therapy that, in two different combinations with other personalized medications, has shown benefits in the treatment of

metastatic stage 

and unresectable or metastatic

This is 

, which inhibits the action of a pathway (called

), responsible for stimulating the growth and proliferation of tumor cells, always in those cases in which the presence of the

is confirmed .

Encorafenib

 is administered as second-line therapy for the treatment of metastatic colorectal cancer in combination with 

, a monoclonal antibody that attacks the epidermal growth factor receptor (EGFR), a protein that is found to be altered in malignant cells, favoring their growth. and multiplication.

A melanoma on the skin of a patient.

Photo: OpenStax College

The approval granted by the National Administration of Drugs, Food and Medical Technology (ANMAT) for this combination use for the treatment of metastatic colorectal cancer with BRAF V600E mutation was based on the results of the BEACON CRC

. 

This work demonstrated that from its use a response rate

(20% vs. 2%) was obtained than that achieved with standard medication.

Overall survival was also higher: 8.4 months versus 5.4 months in the control group, and the median progression-free survival achieved was 4.2 months versus 1.5 months.

The approval of the combination of

 and another drug called

 for the treatment of adult patients with

 unresectable or metastatic

, published in

, a phase 3 trial.

This investigation showed that the new combination obtained a significant improvement in median PFS and overall survival compared to other available drugs, reaching a median PFS of 14.9 months compared to 7.3 months. months of the control group, and a median overall survival of 33.6 months, which doubles the overall survival of the control group. 

“There are few agnostic therapies that exist so far.

We are talking about

, ”confirms Juan Manuel O'Connor, head of the Gastrointestinal Tumors Unit at the Alexander Fleming Institute.

3D structure of a melanoma cell: Photo: Sriram Subramaniam (US National Cancer Institute)

These are

, which up to now have been used to treat tumors in

Although they are approved by ANMAT, it is not so easy to access them since only some prepaid companies authorize them, according to O'Connor in detail when asked by

.

“They have a disease control criterion, not a curative one because they require validation in earlier stages of the disease.

This has to do with it being first tested for advanced disease.

Surely, later on we can verify if it is also effective in the initial stages”, affirms the oncologist.

Regarding the therapy presented by Pfizer, he adds: “The availability of this combination is a clear example of advances in this specific area of ​​patients with metastatic colorectal cancer with the BRAF V600E mutation.

Until now,

”.

Gabriela Cinat, medical oncologist and head of the Melanoma and Sarcoma Unit at the Ángel H. Roffo Institute of Oncology, assures that agnostic therapies aim to interfere

(that is, those responsible for tumor development) to

.

“What is done is

.

This is done through a biopsy, from a tissue sample”, explains Cinet.

Many of the therapies are orally administered, others intravenous.

“The advances made in the treatment of advanced melanoma are very important.

We have managed to control this disease

, but we know that, for the moment, more than half of the patients will die from this cause," warns the oncologist.

And he remarks: "Having new treatment options that can exceed the efficacy or improve the tolerance of already established treatments is always welcome."

Cinat, who participated in the COLUMBUS study, published in The Lancet, maintains in relation to the development of encorafenib and binimetinib: "This combination has clearly demonstrated its efficacy in this scenario and, although it is not compared head-to-head with the other two previously approved , we could say that their effectiveness is similar".

Meanwhile, he adds that "its toxicity profile would seem to be, in general, more tolerable than the others, especially in terms of flu-like symptoms or skin reactions."

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