Current Problems in Cancer最新文献

Introduction

Patients and Methods

Results

Conclusions

Background

Metaplastic breast cancer (MPBC) is a rare variant of breast cancer and most treatment protocols are based on the guidelines for triple negative breast cancer. However, response to standard anthracycline and taxane based chemotherapy is poor. Published literature on use of ifosfamide based chemotherapy in the first line setting for MPBC is scarce.

Patients and methods

We carried out this record based analysis on MPBC patients treated at our institute with the combination of ifosfamide and Adriamycin (IA) as first line therapy. Patients were analysed for the clinical and demographic profile; pathology and treatment details; and treatment outcomes.

Results

Four patients who received IA chemotherapy were evaluated. Three of the four patients were postmenopausal. The median size of the tumor was 7.5 cm, only one patient had a heavy nodal burden and lung was the most common site of metastases seen in all three patients with metastatic disease. Pathology showed heterogenous, mixed histology with high grade tumors. All patients had triple negative tumors. All four patients underwent mastectomy and received IA chemotherapy as per standard doses. One patient had complete response, one had partial response and one patient progressed after 4 cycles of chemotherapy. The patient with localized disease continues to be disease free till date. Grade 3,4 neutropenia and grade 2 anemia was the most common chemotherapy related toxicity.

Conclusion

The response rates in MPBC with IA regimen appear to be similar to the currently used anthracycline-taxane combinations, with slightly more haematological toxicity. Ifosfamide and adriamycin regimen may be considered in MPBC patients as primary or salvage systemic therapy.

Background

Activation of various cancer stem cell pathways are thought to be responsible for treatment failure and loco-regional recurrence in Head and Neck cancer. Hedgehog signaling, a major cancer stem signaling pathway plays a major role in relapse of disease. GLI1, a transcription activator, plays an important role in canonical/non-canonical activation of Hedgehog signaling.

Methods

Data for H&N cancer patients were collected from The Cancer Genome Atlas- H&N Cancer (TCGA-HNSC). GLI1 co-expressed genes in TCGA-HNSC were then identified using cBioPortal and subjected to KEGG pathway analysis by DAVID tool. Network Analyzer and GeneMania plugins from CytoScape were used to identify hub genes and predict a probable pathway from the identified hub genes respectively. To confirm the hypothesis, real-time gene expression was carried out in 75 patients of head and neck cancer.

Results

Significantly higher GLI1 expression was observed in tumor tissues of H&N cancer and it also showed worst overall survival. Using cBioPortal tool, 2345 genes were identified that were significantly co-expressed with GLI1. From which, 15 hub genes were identified through the Network Analyzer plugin in CytoScape. A probable pathway prediction based on hub genes showed the interconnected molecular mechanism and its role in non-canonical activation of Hedgehog pathway by altering the GLI1 activity. The expressions of SHH, GLI1 and AKT1 were significant with each other and were found to be significantly associated with Age, Lymph-Node status and Keratin.

Conclusion

The study emphasizes the critical role of the Hh pathway's activation modes in H&N cancer, particularly highlighting the non-canonical activation through GLI1 and AKT1. The identification of SHH, GLI1 and AKT1 as potential diagnostic biomarkers and their association with clinic-pathological parameters underscores their relevance in prognostication and treatment planning. Hh pathway activation through GLI1 and its cross-talk with various pathways opens up the possibility of newer treatment strategies and developing a panel of therapeutic targets in H&N cancer patients.

Rearrangements involving the ROS1 gene are infrequent in non-small cell lung cancer (NSCLC) but represent an important targetable driver alteration. Occurring most commonly in patients with adenocarcinoma who have a light or never smoking history, ROS1 rearrangements can be identified by either fluorescence in-situ hybridization (FISH) or next-generation sequencing techniques. Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.

Advancements in somatostatin receptor (SSTR) targeted imaging and treatment of well-differentiated neuroendocrine tumors (NETs) have revolutionized the management of these tumors. This comprehensive review delves into the current practice, discussing the use of the various FDA-approved SSTR-agonist PET tracers and the predictive imaging biomarkers, and elaborating on Lu177-DOTATATE peptide receptor radionuclide therapy (PRRT) including the evolving areas of post-therapy imaging practices, PRRT retreatment, and the potential role of dosimetry in optimizing patient treatments. The future directions sections highlight ongoing research on investigational PET imaging radiotracers, future prospects in alpha particle therapy, and combination therapy strategies.

Functional neuroendocrine neoplasms (NENs) are those associated with specific symptoms related to the hormonal secretion of the NENs. Although less than 25 % of NENs are functional at diagnosis,¹ the associated syndromes significantly increase the patient burden of disease. Management of hormonal NEN symptoms may involve tumor resection or other reduction strategies (e.g., chemotherapy, embolotherapy, etc), but also specific therapies directed at decreasing hormonal synthesis, secretion, or end-organ effects. In this review, we focus on specific symptomatic management of many of the NEN syndromes, which may be pursued in addition to management primarily directed at tumor bulk and growth. A continued focus on symptom management related to the hormonal secretions of NENs, in the context of other efforts to reduce tumor bulk and growth, could significantly improve patient wellbeing.