Mutation analysis of second primary tumors in head and neck cancer in Taiwanese patients through next-generation sequencing

Head and neck cancer has poor overall survival. Patients with head and neck cancer more frequently develop second primary tumors than do patients with other cancers, leading to a poor prognosis. In this study, we used next-generation sequencing to analyze and compare mutations between first tumors and second tumors in head and neck cancer. We retrieved tumor tissues collected from 15 patients who were diagnosed twice as having cancer. We used driver gene and trunk mutations to distinguish between recurrent cancer and primary cancer in oral cancer. We observed unique driver gene mutations in three patients with an initial clinical diagnosis of recurrent cancer; hence, we believe that the corresponding patients had primary cancer. Four patients with an initial clinical diagnosis of primary cancer were found to actually have recurrent cancer according to our results. Three (75%) patients with recurrent cancer demonstrated NUP98 mutations. NUP98 mutations may be a new biomarker for diagnosing recurrent oral cancer. Genetic testing can be used to enhance the accuracy of clinical diagnosis.

Circulating tumor cells and circulating cancer stem cells and their detection by the method of flow cytometry

This review describes the circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs). CCSCs are one of the main initiators of recurrent cancer and thus make them an important target for the development of new treatment methods. CTCs are relatively new biomarkers for the early diagnosis of metastasis. CTCs provide doctors with valuable information about each stages of cancer treatments: diagnostic of early-stage disease, early detection of recurrent cancer, the efficiency of chemotherapy, and makes it possible to select an individual sensitive drug.The most informative and frequently used markers for the detection of CSCs and CSCs were described. The mechanism of two models of tumor formation is considered: clonal and hierarchical. The known mechanisms of epithelial-mesenchymal transition of tumor cells are described. The most widely used specific cell surface markers for the detection and isolation of CTCs and CCSCs are described. The efficiency of a sensitive high-precision method of multicolor flow cytometry using specific fluorescent dye-labeled monoclonal antibodies for the detection of CCSCs and CTCs in the blood of cancer patients is analyzed. Detection of CTCs and CCSCs provides important information for the early diagnosis of metastasis and open a possibility to personalized treatment, and to monitoring of all stages cancers.

Personalized Armored TCR-Redirected T Cell Therapy for Liver/Organ Transplant with Recurrent Cancer

Hepatitis B virus-related hepatocellular carcinoma recurrence after liver transplantation (LT) is notoriously difficult to manage and fatal. As a therapeutic option, adoptive cell therapy with HBV-specific TCR-redirected T cells could be employed to target and control relapses in these patients. However, indispensable immunosuppressive medications post-transplantation can significantly hinder the optimum efficacy of such therapy in the clinic. Here we report a new class of Armored TCR T cells which are able to attack recurrent cancer cells in liver transplanted recipients, while temporarily evading immunosuppressant drugs. We believe this strategy could open up new opportunities for treating pathologies under immunosuppressant treatment.

Therapeutic Implications of Germline Testing in Patients With Advanced Cancers

PURPOSE Tumor mutational profiling is increasingly performed in patients with advanced cancer. We determined the extent to which germline mutation profiling guides therapy selection in patients with advanced cancer. METHODS Patients with cancer undergoing tumor genomic profiling were prospectively consented for germline cancer predisposition gene analysis (2015-2019). In patients harboring germline likely pathogenic or pathogenic (LP/P) alterations, therapeutic actionability was classified using a precision oncology knowledge base. Patients with metastatic or recurrent cancer receiving germline genotype–directed therapy were determined. RESULTS Among 11,947 patients across > 50 malignancies, 17% (n = 2,037) harbored a germline LP/P variant. By oncology knowledge base classification, 9% (n = 1042) had an LP/P variant in a gene with therapeutic implications (4% level 1; 4% level 3B; < 1% level 4). BRCA1/2 variants accounted for 42% of therapeutically actionable findings, followed by CHEK2 (13%), ATM (12%), mismatch repair genes (11%), and PALB2 (5%). When limited to the 9,079 patients with metastatic or recurrent cancer, 8% (n = 710) harbored level 1 or 3B genetic findings and 3.2% (n = 289) received germline genotype–directed therapy. Germline genotype–directed therapy was received by 61% and 18% of metastatic cancer patients with level 1 and level 3B findings, respectively, and by 54% of BRCA1/2, 75% of mismatch repair, 43% of PALB2, 35% of RAD51C/D, 24% of BRIP1, and 19% of ATM carriers. Of BRCA1/2 patients receiving a poly(ADP-ribose) polymerase inhibitor, 45% (84 of 188) had tumors other than breast or ovarian cancer, wherein the drug, at time of delivery, was delivered in an investigational setting. CONCLUSION In a pan-cancer analysis, 8% of patients with advanced cancer harbored a germline variant with therapeutic actionability with 40% of these patients receiving germline genotype–directed treatment. Germline sequence analysis is additive to tumor sequence analysis for therapy selection and should be considered for all patients with advanced cancer.

What is the Effect of Splenic Involvement Sites in Advanced Ovarian, Tubal and Peritoneal Epithelial Cancer on Overall Survival?

Purpose: In this study, we evaluated the significance of parenchymal, hilar, and capsular involvement of the spleen with regard to the overall survival of patients who required a splenectomy during cytoreduction procedures for primary or recurrent cancer. Methods: This study includes data from 287 patients who underwent a splenectomy during optimal cytoreduction in epithelial ovarian, tubal, and peritoneal cancers. Spleen involvement regions were divided into four main groups, and the groups were classified as capsule, hilus, capsule + hilus, and other region involvement (paranchyma ± other(s) involvement site). The overall survivals of these four groups were compared.Results: The mean age of the study group was 57.9 years, and the mean follow-up period of the patients was 43.2 months. The splenic involvement site was most frequently observed as hilus + capsule (42.2% n:121). Splenic parenchymal involvement was present in 27.9% (n: 80) of the patients. The overall survival for patients was 42 months. In the subgroup analysis, the worst overall survival was found in the group with capsule involvement at 33 months.Conclusion: While parenchymal involvement of the spleen was considered to be stage IV according to FIGO staging, we could not detect low overall survival in patients with parenchymal involvement in our study. Our study, which has the largest number in the literature examining the relationship between splenic involvement and overall survival, can provide a remarkable perspective on the relationship between parenchymal involvement of the spleen and prognosis.

Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma

Progesterone resistance can significantly restrict the efficacy of conservative treatment for patients with endometrial cancer who wish to preserve their fertility or those who suffer from advanced and recurrent cancer. SREBP1 is known to be involved in the occurrence and progression of endometrial cancer, although the precise mechanism involved remains unclear. In the present study, we carried out microarray analysis in progesterone-sensitive and progesterone-resistant cell lines and demonstrated that SREBP1 is related to progesterone resistance. Furthermore, we verified that SREBP1 is over-expressed in both drug-resistant tissues and cells. Functional studies further demonstrated that the inhibition of SREBP1 restored the sensitivity of endometrial cancer to progesterone both in vitro and in vivo, and that the over-expression of SREBP1 promoted resistance to progesterone. With regards to the mechanism involved, we found that SREBP1 promoted the proliferation of endometrial cancer cells and inhibited their apoptosis by activating the NF-κB pathway. To solve the problem of clinical application, we found that Fatostatin, an inhibitor of SREBP1, could increase the sensitivity of endometrial cancer to progesterone and reverse progesterone resistance by inhibiting SREBP1 both in vitro and in vivo. Our results highlight the important role of SREBP1 in progesterone resistance and suggest that the use of Fatostatin to target SREBP1 may represent a new method to solve progesterone resistance in patients with endometrial cancer.