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Ovarian cancer is one of the common malignant tumors of the female reproductive system and one of the important causes of death from gynecological malignancies.
It is said that ovarian cancer is difficult to treat.
The reason is that the symptoms of early patients are hidden without any discomfort.
Once discovered, it is late and it is more difficult to treat.
Why is it difficult to treat? Speaking of it, it is because the development of ovarian treatment is extremely slow.
Since the introduction of cisplatin in the 1970s, the OS of some patients with ovarian cancer has been improved by about 6 months.
So far, platinum-based chemotherapy has been established.
In the mid-1980s, carboplatin, an analog of cisplatin, was born.
It immediately replaced cisplatin because of its less toxicity and the same effect.
In the 1990s, the combination therapy of paclitaxel and platinum drugs appeared, which was a major advancement and further improved OS.
In the following 30 years, there has been no major clinical breakthrough, and the treatment of ovarian cancer has stagnated.
In recent years, with the rapid development of precision medicine, various new therapies have emerged one after another, and the 30-year dilemma has finally been broken! However, most of these emerging therapies require precise screening of the population.
Taking the latest NCCN guidelines for ovarian cancer as an example, biomarkers such as BRCA, HRD, NTRK, MSI, and TMB have all been recommended.
BRCA gene detection opens the door to the "cure" of ovarian cancer.
BRCA is a very important tumor suppressor gene, which has a repair function mainly in the process of DNA mutation.
BRCA gene mutation is highly related to the incidence of ovarian cancer.
People with BRCA gene mutations have a lifetime risk of ovarian cancer as high as 11%-39%, while the general population’s risk of cancer is only 1.
3%.
BRCA-mutated ovarian cancer patients have defects in the repair function of homologous recombination.
PARP inhibitors can inhibit the repair of tumor cell DNA and promote tumor cell apoptosis through synthetic lethal effects. The latest SOLO-1 data shows that for newly diagnosed ovarian cancer patients with BRCA mutations, the benefits of maintenance therapy with the PRAP inhibitor olaparib for 2 years can continue until the end of the treatment, and nearly half of the patients will be treated after 5 years.
Progression-free events, and more than half of patients who reached CR at baseline achieved 5-year relapse-free survival.
It is worth mentioning that the mutation rate of BRCA gene in ovarian cancer patients in my country can reach more than 20%.
In addition, these patients have also been included in the scope of medical insurance reimbursement.
Based on this, it is of great benefit to carry out BRCA1/2 genetic testing when the patient is diagnosed.
HRD detection broadens the path to precision in ovarian cancer As mentioned above, “BRCA-mutated ovarian cancer patients have defects in homologous recombination repair.
PARP inhibitors can inhibit tumor cell DNA repair and promote tumor cell apoptosis through synthetic lethal effects "However, in addition to BRCA, there are many other factors that can cause homologous recombination repair defects (HRD).
In fact, many genes in the homologous recombination (HR) pathway are closely related to the sensitivity of PARP inhibitors, and there are even many unknown factors.
It can be seen that population screening for PRAP inhibitors should not be limited to BRCA.
Based on current research, patients with homologous recombination repair defects (HRD) are prone to instability in their genomes, which are called "scars.
"
By detecting whether there is a "scar", you can know whether the patient has homologous recombination repair function defects, and then you can screen suitable ovarian cancer patients to receive PARP inhibitor maintenance treatment.
The PAOLA-1 study clearly shows that HRD-positive ovarian cancer patients can benefit from the maintenance treatment of olaparib combined with bevacizumab.
It should be pointed out that in the PAOLA-1 study, about 50% of the people with positive ovarian cancer screened by the HRD test have greatly expanded the use of PARP inhibitors.
NTRK, MSI, and TMB gene detection, pan-cancer seed therapy "overweight" ovarian cancer.
In the field of tumor treatment, there are several drugs that are not restricted by cancer types.
Their indications only look at the gene phenotype, and they are known as broad-spectrum anticancer drugs.
These include entritinib and larotinib for the treatment of patients with NTRK gene fusion-positive tumors, and pembrolizumab for the treatment of patients with microsatellite instability (MSI-H) or high tumor mutation burden (TMB).
Based on this, the latest edition of the NCCN Guidelines lists NTRK, MSI, and TMB as recommended testing items.
Once the test is positive, the corresponding drugs can be considered for treatment.
However, unlike BRCA and HRD tests, the positive rates of NTRK, MSI, and TMB are low, and the target population of drugs is small.
There is no large-scale data summary analysis for NTRK mutations in ovarian cancer.
In large-scale data statistics, the population of MSI-H ovarian patients is only 1~2%, and the proportion of TMB-H is less than 2%.
In one study, only one of 64 patients with ovarian cancer had a TMB greater than 10.
It is not an exaggeration to say that NTRK, MSI, and TMB are all one of a hundred.
In clinical practice, there are many types of genetic testing items, various genes, various combinations, and sometimes large and comprehensive testing, which may not be the right choice.
Take ovarian cancer for example, a BRCA test has a positive rate of 20%.
If you expand the test for an HRD, you can reach a positive rate of 50%.
And choosing the super package (not including HRD test) also has a positive rate of 20%+ (BRCA+NTRK+MSI+TMB).
Let's combine the two factors of the price of each test and the availability of corresponding drugs: 1) The price of large package testing is often around 20,000, single BRCA testing is only three to five thousand, and HRD testing is only about 10,000; 2) PARP inhibitors are currently in the medical insurance catalog, and NTRK inhibitors and PD-1 inhibitors are still at their own expense.
Among them, NTRK inhibitors can easily cost millions of treatment for a year, which basically directly discourages patients. Therefore, in ovarian cancer, based on the three factors of positive rate, test price, and drug availability, BRCA and HRD are ideal markers and should be checked! Reference: NCCN guideline-ovarian cancer-2021V1Petrucelli N, Daly MB, Pal T.
BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.
1998 Sep 4 [Updated 2016 Dec 15].
2020 ESMOWafik S.
El〥eiry, et al .
"The current state of molecular testing in the treatment of patients with solid tumors, 2019.
" CA A Cancer Journal for Clinicians 69.
15(2019).
Liu, YL, et al.
"BRCA Mutations, Homologous DNA Repair Deficiency, Tumor Mutational Burden , and Response to Immune Checkpoint Inhibition in Recurrent Ovarian Cancer.
" JCO Precision Oncology 4.
4(2020):665-679.
Source: Molecular Pathology Online
It is said that ovarian cancer is difficult to treat.
The reason is that the symptoms of early patients are hidden without any discomfort.
Once discovered, it is late and it is more difficult to treat.
Why is it difficult to treat? Speaking of it, it is because the development of ovarian treatment is extremely slow.
Since the introduction of cisplatin in the 1970s, the OS of some patients with ovarian cancer has been improved by about 6 months.
So far, platinum-based chemotherapy has been established.
In the mid-1980s, carboplatin, an analog of cisplatin, was born.
It immediately replaced cisplatin because of its less toxicity and the same effect.
In the 1990s, the combination therapy of paclitaxel and platinum drugs appeared, which was a major advancement and further improved OS.
In the following 30 years, there has been no major clinical breakthrough, and the treatment of ovarian cancer has stagnated.
In recent years, with the rapid development of precision medicine, various new therapies have emerged one after another, and the 30-year dilemma has finally been broken! However, most of these emerging therapies require precise screening of the population.
Taking the latest NCCN guidelines for ovarian cancer as an example, biomarkers such as BRCA, HRD, NTRK, MSI, and TMB have all been recommended.
BRCA gene detection opens the door to the "cure" of ovarian cancer.
BRCA is a very important tumor suppressor gene, which has a repair function mainly in the process of DNA mutation.
BRCA gene mutation is highly related to the incidence of ovarian cancer.
People with BRCA gene mutations have a lifetime risk of ovarian cancer as high as 11%-39%, while the general population’s risk of cancer is only 1.
3%.
BRCA-mutated ovarian cancer patients have defects in the repair function of homologous recombination.
PARP inhibitors can inhibit the repair of tumor cell DNA and promote tumor cell apoptosis through synthetic lethal effects. The latest SOLO-1 data shows that for newly diagnosed ovarian cancer patients with BRCA mutations, the benefits of maintenance therapy with the PRAP inhibitor olaparib for 2 years can continue until the end of the treatment, and nearly half of the patients will be treated after 5 years.
Progression-free events, and more than half of patients who reached CR at baseline achieved 5-year relapse-free survival.
It is worth mentioning that the mutation rate of BRCA gene in ovarian cancer patients in my country can reach more than 20%.
In addition, these patients have also been included in the scope of medical insurance reimbursement.
Based on this, it is of great benefit to carry out BRCA1/2 genetic testing when the patient is diagnosed.
HRD detection broadens the path to precision in ovarian cancer As mentioned above, “BRCA-mutated ovarian cancer patients have defects in homologous recombination repair.
PARP inhibitors can inhibit tumor cell DNA repair and promote tumor cell apoptosis through synthetic lethal effects "However, in addition to BRCA, there are many other factors that can cause homologous recombination repair defects (HRD).
In fact, many genes in the homologous recombination (HR) pathway are closely related to the sensitivity of PARP inhibitors, and there are even many unknown factors.
It can be seen that population screening for PRAP inhibitors should not be limited to BRCA.
Based on current research, patients with homologous recombination repair defects (HRD) are prone to instability in their genomes, which are called "scars.
"
By detecting whether there is a "scar", you can know whether the patient has homologous recombination repair function defects, and then you can screen suitable ovarian cancer patients to receive PARP inhibitor maintenance treatment.
The PAOLA-1 study clearly shows that HRD-positive ovarian cancer patients can benefit from the maintenance treatment of olaparib combined with bevacizumab.
It should be pointed out that in the PAOLA-1 study, about 50% of the people with positive ovarian cancer screened by the HRD test have greatly expanded the use of PARP inhibitors.
NTRK, MSI, and TMB gene detection, pan-cancer seed therapy "overweight" ovarian cancer.
In the field of tumor treatment, there are several drugs that are not restricted by cancer types.
Their indications only look at the gene phenotype, and they are known as broad-spectrum anticancer drugs.
These include entritinib and larotinib for the treatment of patients with NTRK gene fusion-positive tumors, and pembrolizumab for the treatment of patients with microsatellite instability (MSI-H) or high tumor mutation burden (TMB).
Based on this, the latest edition of the NCCN Guidelines lists NTRK, MSI, and TMB as recommended testing items.
Once the test is positive, the corresponding drugs can be considered for treatment.
However, unlike BRCA and HRD tests, the positive rates of NTRK, MSI, and TMB are low, and the target population of drugs is small.
There is no large-scale data summary analysis for NTRK mutations in ovarian cancer.
In large-scale data statistics, the population of MSI-H ovarian patients is only 1~2%, and the proportion of TMB-H is less than 2%.
In one study, only one of 64 patients with ovarian cancer had a TMB greater than 10.
It is not an exaggeration to say that NTRK, MSI, and TMB are all one of a hundred.
In clinical practice, there are many types of genetic testing items, various genes, various combinations, and sometimes large and comprehensive testing, which may not be the right choice.
Take ovarian cancer for example, a BRCA test has a positive rate of 20%.
If you expand the test for an HRD, you can reach a positive rate of 50%.
And choosing the super package (not including HRD test) also has a positive rate of 20%+ (BRCA+NTRK+MSI+TMB).
Let's combine the two factors of the price of each test and the availability of corresponding drugs: 1) The price of large package testing is often around 20,000, single BRCA testing is only three to five thousand, and HRD testing is only about 10,000; 2) PARP inhibitors are currently in the medical insurance catalog, and NTRK inhibitors and PD-1 inhibitors are still at their own expense.
Among them, NTRK inhibitors can easily cost millions of treatment for a year, which basically directly discourages patients. Therefore, in ovarian cancer, based on the three factors of positive rate, test price, and drug availability, BRCA and HRD are ideal markers and should be checked! Reference: NCCN guideline-ovarian cancer-2021V1Petrucelli N, Daly MB, Pal T.
BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.
1998 Sep 4 [Updated 2016 Dec 15].
2020 ESMOWafik S.
El〥eiry, et al .
"The current state of molecular testing in the treatment of patients with solid tumors, 2019.
" CA A Cancer Journal for Clinicians 69.
15(2019).
Liu, YL, et al.
"BRCA Mutations, Homologous DNA Repair Deficiency, Tumor Mutational Burden , and Response to Immune Checkpoint Inhibition in Recurrent Ovarian Cancer.
" JCO Precision Oncology 4.
4(2020):665-679.
Source: Molecular Pathology Online
