Compounds with CAS RN 2097133-17-8, CAS RN 2778223-52-0 and CAS RN 35277-02-2 can be used to synthesize Pralsetinib. Pralsetinib, sold under the name GAVRETO, was developed by Blueprint Medicines Corporation for adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC).

What is RET+ non-small cell lung cancer

RET+ non-small cell lung cancer (NSCLC) is a specific subtype of non-small cell lung cancer characterized by genetic alterations involving the RET gene.

1.     Non-Small Cell Lung Cancer (NSCLC):

NSCLC is the most common type of lung cancer, accounting for approximately 85% of all lung cancer cases. It is categorized as "non-small cell" because the cancer cells appear different under a microscope compared to "small cell" lung cancer cells.

Jain, Anisha S., et al. "Everything old is new again: Drug repurposing approach for non-small cell lung cancer targeting MAPK signaling pathway." Frontiers in Oncology 11 (2021): 741326.

NSCLC includes several subtypes, one of which is RET+ NSCLC.

2.     RET (Rearranged during Transfection) Gene:

The RET gene is a normal part of our DNA responsible for encoding a protein that plays a crucial role in cell growth and development, particularly in the nervous system. However, in some cases, alterations or mutations can occur in the RET gene. These alterations can lead to the production of a faulty or overactive RET protein, which can contribute to the development of cancer when it occurs in lung tissue.

3.     RET+ NSCLC:

RET+ NSCLC refers to non-small cell lung cancer that has a specific genetic alteration involving the RET gene. In RET+ NSCLC, there is a rearrangement or fusion of the RET gene with another gene. This fusion results in the abnormal activation of the RET protein, leading to uncontrolled cell growth and the development of cancerous tumors in the lungs.

It's important to note that RET gene alterations are not exclusive to lung cancer and can also occur in other types of cancer, such as thyroid cancer. However, when RET gene alterations are identified in NSCLC, it becomes crucial information for treatment decisions.

Global Disease Burden

According to the International Agency for Research on Cancer (IARC), in 2020, the estimated number of newly diagnosed cases of cancer worldwide is between 18 and 19 million, and the global 5-year prevalence is about 44 million. In 2020, lung cancer accounted for more than 11% of new diagnoses (more than 2.2 million new cases) and accounted for approximately 1.8 million deaths globally of all sexes.

Lung cancers are a heterogeneous group of cancers that are divided into two major histologic categories based on the type of cells they form non-small cell lung cancer and small cell lung cancer.

Fortunately for patients, there have been major advances in the understanding of NSCLC over the past decade. Screening was introduced with the aim of early detection. In the United States, for example, the National Lung Screening Trial found that the use of low-dose chest computed tomography in high-risk populations was associated with a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality.

In addition, the 5-year survival rate increased slightly, from 15.6% in 2011 to 19.4% in 2019. This modest improvement can be attributed to increased early detection, as well as advances in treatments such as thoracoscopic surgery, radiation therapy, immunotherapy, and targeted therapy.

How to Treat This Disease

Targeted therapies, including drugs such as Selpercatinib and Pralsetinib have been developed to specifically address RET+ NSCLC by inhibiting the abnormal activity of the RET protein. These targeted therapies have shown promise in treating this subtype of lung cancer and have provided new options for patients.

1. Selpercatinib (Retevmo): Selpercatinib is a drug targeting RET, ROS1, and ALK fusion genes, which has been approved for the treatment of a variety of RET mutation-associated cancers, such as medullary thyroid carcinoma (MTC) and non-small cell lung cancer (NSCLC).

2. Pralsetinib (Gavreto): Pralsetinib is an inhibitor specifically for RET mutation-driven medullary thyroid carcinoma (MTC) and non-small cell lung cancer (NSCLC).

Market Overview of Pralsetinib

Mechanism of Action: Pralsetinib is a tyrosine kinase inhibitor (TKI) that targets the RET protein. By inhibiting RET, it disrupts the signaling pathways responsible for cancer cell growth, thus offering a targeted approach to cancer treatment.

Clinical Trials: Pralsetinib underwent rigorous clinical trials to establish its safety and efficacy. These trials demonstrated high response rates and improved progression-free survival in patients with RET-altered cancers.

Regulatory Approvals: Pralsetinib has received regulatory approvals, including approval by the U.S. Food and Drug Administration (FDA) and other health authorities in various countries, for its indicated uses. This signifies its safety and efficacy for patients with RET-altered cancers.

Market Access: Pralsetinib is available to eligible patients under its brand name, Gavreto, and is prescribed based on the specific cancer diagnosis and treatment plan determined by healthcare professionals.

References

[1]Desilets A, Repetto M, Yang R S, et al. RET -Altered Cancers—A Tumor-Agnostic Review of Biology, Diagnosis, and Targeted Therapy Activity[J]. Cancers,2023,15(16).

[2]Clara B,Lucas T,Sébastien F, et al. Therapeutic strategies for non-small cell lung cancer: Experimental models and emerging biomarkers to monitor drug efficacies[J]. Pharmacology and Therapeutics,2023,242.

[3]Lin J, Liu S, McCoach C, et al. Mechanisms of Resistance to Selective RET Tyrosine Kinase Inhibitors in RET Fusion-Positive Non-Small Cell Lung Cancer[J]. Annals of Oncology,2020,31(12).

[4] Jain, Anisha S., et al. "Everything old is new again: Drug repurposing approach for non-small cell lung cancer targeting MAPK signaling pathway." Frontiers in Oncology 11 (2021): 741326.