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Many people who have been diagnosed with NED cancer are wondering why they have not been referred for routine imaging exams. While PET scans can detect a recurrence earlier than symptoms, the benefits of earlier detection are, not associated with increased survival. While hearing the news of NED cancer is a relief, people often experience complex emotions as they begin a new phase of their cancer journey. They may face uncertainty, lingering side effects, and major changes to their life.
Neuroendocrine differentiation (NED)
The relationship between neuroendocrine differentiation and cancer is still not clear. However, it is, known that alterations in a gene that drives neuroendocrine differentiation have an improved prognosis. These genes include EZH2, SOX2, and REST. However, further research is, needed to determine the functional role of these genes in cancer development.
Several studies have shown a significant relationship between NEPCs and p53. In addition, several genes have been found to be associated with NEPC, including Rb. In addition, AURKA, MYCN, and SRRM4 were also associated with NEPC. Interestingly, the loss of the Rb gene was, observed in more than 50% of NEPCs. This association indicates that loss of p53 and Rb can induce a stem-cell-like state. In addition, SOX2 promotes lineage plasticity in cancer cells.
Neuroendocrine differentiation in cancer is, conceptually defined as the presence of neurosecretory granules in neoplastic cells. In addition, tumors displaying NE differentiation show architectural patterns similar to nonneoplastic NE cells. These tumors usually exhibit a granular cytoplasm and a nesting or trabecular growth pattern. Breast cancers exhibiting NE differentiation include mucinous carcinomas and solid papillary carcinomas.
In addition, neuroendocrine differentiation in prostate cancer is, thought to be a mechanism of drug resistance. It has been shown that prostate cancer cells can develop neuroendocrine differentiation as a strategy to resist new antiandrogen therapies. While de novo small cell NE cancer is rare, a subset of prostate adenocarcinoma patients develop neuroendocrine features at a later stage of the disease.
The highest-level lncRNA in NEPC is SSTR5-AS1. This protein interacts with KDM4B, a key molecule in AR signaling. Moreover, it regulates transcriptional activity in prostate adenocarcinoma and neuroblastoma cells. It also interacts with N-Myc, which plays a crucial role in neuroendocrine transdifferentiation.
Mechanisms of NED
NED cancer has several mechanisms of development. Fractionated irradiation induces the emergence of CSCs, which are cancer cells that express pluripotency-associated genes. Moreover, fractionated irradiation promotes increased CD133 and CD138 mRNA expression. Furthermore, fractionated irradiation triggers the re-expression of CD133 and CD138 markers in cancer cells, which may result in the emergence of induced CSCs.
The cells expressing NED markers, such as neuron-specific enolase (NeuN) are, characterized by high levels of cyclic AMP response element binding protein and activating transcription factor 2. These markers have important roles in the regulation of NED. Furthermore, treatment failures may cause by NED-like cells.
NED-170 is an oral combination therapy that targets four essential physiological processes in late-stage cancer. In this way, it improves therapeutic outcomes and enhances patients’ quality of life. The company plans to initiate a Phase 2 clinical trial of NED-170 this year, and hopes to expand the research to other types of cancer in the future.
Treatment options
When patients receive a diagnosis of NED cancer, they should be encouraged to undergo frequent imaging examinations to monitor their progress. PET scans may detect a recurrence before symptoms appear, but this doesn’t necessarily mean improved survival. Although hearing the news of NED is a relief, many people face complicated feelings in the new phase of their cancer journey. They may be confronted with lingering side effects, uncertainty, or even drastic life changes.
Treatment options for NED cancer include medical treatments, counseling, and psychological support. After completing treatment, patients may continue to experience side effects of treatment such as shortness of breath or fatigue. Sometimes, these symptoms will remain for years. Some people may even experience scanxiety. For these reasons, they should be sure to talk with their healthcare team to find a treatment option that fits their needs and their lifestyle.
Patients with NED had longer median survival than patients with metastatic disease, but direct comparisons of these groups are, limited by a guarantee of time. Nevertheless, patients who reached NED had a ninety-two-month survival period, compared with seven years or nine years for patients with nonmetastatic disease. In addition, patients who experienced NED had survival rates of 98% at one year, 89% at three years, 77% at five years, and 39% at 10 years.
In addition to improving survival, the presence of only one site of the disease has also been associated with a higher risk of NED. However, the risk of death increased by 18% with each additional site. A recent study on seven hundred patients found that single-organ involvement was, associated with improved outcomes, while cancer spread to multiple organs was, associated with a greater risk of death. While single-organ involvement is, not considered an indication of NED, the presence of a single organ may reflect tumor plasticity.
The goal of chemotherapy is to kill the cancer cells and stop its spread. The doctor may prescribe regular chemotherapy as a maintenance treatment, which will help to control the spread of the cancer and prolong a patient’s life. In addition to chemotherapy, patients can receive palliative care. This type of care relieves the side effects associated with chemo.
PFS
The PFS for NED cancer is a measure of how long patients will survive after treatment ends. While the median PFS for all patients was 27 months, it ranged from 0 to 134 months for patients who achieved NED. Patients who underwent trastuzumab were more likely to achieve PFS than those who did not receive the drug.
The goal of local therapy is to achieve no evidence of disease or non-progressive residual disease. NPRD is, defined as less than three sites of progressive disease. No patient could have more than three sites of progression, and the NPRD category included any number of tumors that regressed or remained stable. Patients with NPRD are, required to undergo serial imaging evaluations to ensure that they remain in a stable state.
Patients who achieved NED status showed significantly longer median survival times than those with advanced stage or metastatic disease. However, direct comparisons are biased because patients were, guaranteed a time frame. In one study, patients who achieved NED status had a median survival of 102 months. At 1 year, they had a 98% survival rate. The median survival time at three years and five years was 89%, whereas their PFS was 39% at 10 years.
The results of the MYSTIC study were disappointing for AstraZeneca, which had hoped to become a leader in the oncology field and beat its patent cliffs. The company’s share price plunged 15% on the news. It worked hard to temper investors’ expectations and warned that missing the PFS did not mean that the drug failed.
In a study involving more than 700 patients, single-organ involvement was, associated with better survival than multiple organ involvement. For each additional site of disease, the risk of death increased by 18%. Although single-organ involvement does not meet the traditional definition of oligometastatic disease, single-organ involvement may be indicative of tumor plasticity.
In a similar study, patients with a primary tumor that has not responded to chemotherapy had a similar PFS to those who had received chemotherapy. The PFS for these patients was not significantly lower than that of the people with sun-exposed cancer, but their DSS was lower. In addition, patients who had a major thoraco-abdominal surgical resection and monotherapy had similar PFS.
