DEFINITION
Precision medicine (PM) is a medical paradigm that supports the personalization of healthcare by adjusting medical judgments, interventions, procedures, or products to a particular patient population as an alternative to employing a one-drug-fits-all strategy.(1)
This article will cover a case that was successfully treated using precision therapeutics as well as a list of FDA-approved precision medications.
FDA Approved Precision Medicine
MedicationIndicationTargeted PopulationBiomarkerTrastuzumabBreast CancerHER2-positiveHER2 protein overexpressionImatinibChronic Myeloid LeukemiaBCR-ABL gene fusionBCR-ABL geneVemurafenibMelanomaBRAF V600E mutationBRAF V600E mutationOsimertinibNon-Small Cell Lung CancerEGFR T790M mutationEGFR T790M mutationPembrolizumabVarious CancersPD-L1 expressionPD-L1 protein expressionIvacaftorCystic FibrosisSpecific CFTR gene mutationsCFTR gene mutationsCrizotinibNon-Small Cell Lung CancerALK gene rearrangementALK gene rearrangementLarotrectinibVarious CancersNTRK gene fusionNTRK gene fusionOlaparibOvarian CancerBRCA gene mutationBRCA gene mutationNivolumabVarious CancersPD-1 expressionPD-1 protein expressionEntrectinibVarious CancersNTRK gene fusion, ROS1 gene fusionNTRK gene fusion, ROS1 gene fusionAtezolizumabBladder CancerPD-L1 expressionPD-L1 protein expressionTisagenlecleucelLeukemia/LymphomaCD19 expressionCD19 protein expressionRibociclibBreast CancerHR-positive, HER2-negativeCDK4/6 proteinBrigatinibNon-Small Cell Lung CancerALK gene rearrangementALK gene rearrangement
The medications listed in the table has been approved by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in precision medicine and are widely used in clinical practice. [2]
A Case Report on Personalized Medicine:
Targeted Therapy for Recurrent Neuroblastoma(NB).
This case report provides a concrete illustration of targeted therapy for the recurrence of neuroblastoma in order to highlight the potential of personalized medicine in the treatment of advanced cancers.
Ten years after the initial diagnosis of high-risk neuroblastoma, the patient, in this case, experienced a late recurrence of the disease. In accordance with the NB-HR-01 protocol, the patient underwent first-line therapy without the benefit of maintenance anti-GD2 immunotherapy.
In September 2009, the patient was diagnosed with bone marrow infiltration, multiple skeletal metastases (limbs, right hemipelvis), left paravertebral undifferentiated NB, MycN not amplified, and thoracic lymph node metastases.
The patient underwent surgery to remove the primary lesion as part of the SIOPEN NB-HR-01 protocol and then underwent four courses of TVD to achieve a partial response (PR).
The next step involved consolidation therapy using busulfan-melphalan and autologous stem cell rescue. The primary lesion was treated with radiotherapy (21 Gy), and then cis-retinoic acid was used as a maintenance treatment.
The patient was fully in remission when therapy was finished, and the follow-up period started in March 2011.
The patient first complained of left arm pain and swelling in April 2020. An MRI showed a mass that involved the distal humerus and penetrated the soft tissues for about 6 cm and the medullary canal for about 9 cm.
On grounds of possible NB recurrence, a CT-guided needle biopsy was carried out. PHOX-2B negative, MycN not amplified, S100 positive, ALK-positive, and c-Myc negative were all suggested by histopathological analysis to be immunophenotypical characteristics of undifferentiated NB.
Six potential candidate genes were found through whole-exome sequencing (WES) on the tumor and normal tissue, but the PSMC2 gene mutation c.A484G was chosen for targeted therapy with bortezomib. The disease had spread widely throughout the soft tissues of the left arm, as well as to numerous skeletal metastases and axillary lymph nodes, according to a restaging of the condition.
Two courses of ICE chemotherapy were recommended as part of a customized second-line treatment regimen, and this resulted in significant clinical improvement and the disappearance of pathological uptake at all disease sites on 123I-MIBG scintigraphy.
A third round of ICE chemotherapy was administered to the patient in September 2020, but a pathological signal was still visible in the left arm. This chemotherapy caused grade 2 renal tubular toxicity and grade 3 hematological toxicity.
A complete response to all known lesions was observed after three rounds of chemotherapy, with a residual signal alteration in the upper arm. Based on the molecular alteration (PSMC2 gene) found in the tumor tissue collected after relapse within the PREME project, off-label target therapy was administered with two courses of Bortezomib and Irinotecan and two courses of TEMIRI (Temozolomide and Irinotecan).
A disease assessment was carried out in January 2021 using 123I-MIBG scintigraphy, MRI, and bone marrow analysis, and the results revealed complete remission (CR).
This case exemplifies the potential of personalized medicine for the treatment of advanced cancers, as WES was able to identify a particular genetic mutation that permitted targeted therapy with Bortezomib and a customized second-line treatment regimen that brought the patient's cancer completely into remission. [3]
SUMMING UP
In summary, precision medicine has come a long way since its inception and is still developing quickly. A promising advancement in medical science is its potential to revolutionize healthcare by offering personalized treatment options based on a person's particular genetic makeup.
Precision medicine has the potential to improve patient satisfaction, health outcomes, and overall healthcare system efficiency as it becomes more and more integrated into healthcare systems.
Although there are still obstacles to be overcome, the development of precision medicine so far has shown the profound influence that this strategy can have on patient care.
It is exciting to think about a time when every patient can get a personalized treatment plan that is created to maximize their health and well-being as research and development in this area continues.
References
1.wikipedia on precision medicine.
1. Pastorino F, Capasso M, Brignole C, Giglio S, Bensa V, Cantalupo S, Lasorsa VA, Tondo A, Mura R, Sementa AR, Garaventa A, Ponzoni M, Amoroso L. Italian Precision Medicine in Pediatric Oncology: Moving Beyond Actionable Alterations. International Journal of Molecular Sciences. 2022; 23(19):11236. https://doi.org/10.3390/ijms231911236
2.US FDA website
3..https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656435/