World Journal of Oncology最新文献

Background: Aberrant expression and activation of epidermal growth factor receptor (EGFR) resulted in approval of several forms of EGFR inhibitors in the treatment of patients with a wide range of epithelial cancers. However, no EGFR inhibitor has yet been approved for the treatment of patients with brain cancer, indicating that targeting EGFR alone may not be sufficient in some patients.

Methods: In this study, we investigated the role of all members of the EGFR family, other growth factor receptors, cell-cycle proteins, and downstream cell signaling pathways (e.g., mitogen-activated protein kinase (MAPK), serine/threonine protein kinase (AKT), signal transducer and activator of transcription (STAT3), Src, Abelson murine leukemia viral oncogene homolog (Abl)) on the growth of a panel of human brain cancer cell lines (HBCCLs). We examined the growth response of HBCCLs to treatment with 17 targeted agents compared to two cytotoxic drugs.

Results: Of the targeted agents, the irreversible pan-human epidermal growth factor receptor (HER) inhibitors neratinib and afatinib were more effective than erlotinib and lapatinib at inhibiting the growth of all HBCCLs, and the cyclin-dependent kinase (CDK)1/2/5/9 inhibitor dinaciclib was the most potent targeted agent. We found that treatment with Src/Abl/c-kit inhibitor dasatinib, signal transducer and activator of transcription (STAT3) inhibitor stattic, Abl/platelet-derived growth factor receptor (PDGFR)α/vascular endothelial growth factor (VEGFR)2/fibroblast growth factor receptor (FGFR)1 inhibitor ponatinib, and the tropomyosin receptor kinase (TRK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS)/anaplastic lymphoma kinase (ALK) inhibitor entrectinib, also inhibited the growth of all HBCCLs. Interestingly, these agents were more effective in inhibiting growth of HBCCLs when proliferating at a slower rate. In addition to inhibiting the proliferation of HBCCLs, treatment with neratinib, dinaciclib, dasatinib, stattic and trametinib inhibited the migration of brain tumor cell line A172.

Conclusions: Notably, we found that treatment with neratinib in combination with palbociclib (CDK4/6 inhibitor), or miransertib (AKT1/2/3 inhibitor) resulted in synergistic growth inhibition of all HBCCLs. Our results support that repurposing drugs like neratinib in combination with the palbociclib or miransertib may be of therapeutic potential in brain cancer and warrants further investigations.

Background: B-cell lymphoma 2 (Bcl-2), a protein involved in apoptosis, has been proven to have carcinogenic potential and is well documented. With the recent advancement in optical technology, it has become possible to observe subcellular organelles such as mitochondria in real-time without the need for staining. Consequently, we have examined the movement of mitochondria in cancer cells, correlating it with the regulation of Bcl-2.

Methods: Using a tomographic microscope, which can detect the internal structure of cells, we observed lung tumor cells. Cells were exposed to a laser beam (λ = 520 nm) inclined at 45°, and holographic images were recorded up to a depth of 30 µm of reconstruction.

Results: Intriguingly, lung tumor cells rapidly expelled mitochondria upon the attachment of Bcl-2 or B-cell lymphoma extra-large (Bcl-xL) inhibitors. On the other hand, we observed that tumor cells hijack mitochondria from T cells. The hijacked mitochondria were not immediately linked to tumor cell death, but they played a role in assisting granzyme B-induced tumor cell death. Due to lower levels of Bcl-2 and Bcl-xL on the mitochondria of T cells compared to lung tumor cells, immune cells depleted of Bcl-2 and Bcl-xL were co-cultured with the tumor cells.

Conclusions: As a result, a more effective tumor cell death induced by granzyme B was observed. Additionally, further enhanced anticancer immune response was observed in vivo. Together, we show that modified mitochondria of T cells can provide potential novel strategies towards tumor cell death.

Dyspnea is a disabling symptom presented in approximately half of all cancer survivors. From a clinical perspective, despite the availability of pharmacotherapies, evidence-based effective treatments are limited for relieving dyspnea in cancer survivors. Preliminary evidence supports the potential of respiratory muscle training to reduce dyspnea in cancer survivors, although large randomized controlled studies are warranted. The aims of this article were to review the relevant scientific literature on the potential therapeutic role of respiratory muscle training in dyspnea management of cancer survivor, and to identify possible mechanisms, strengths and limitations of the evidence as well as important gaps for future research directions.

Background: The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials.

Methods: Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed.

Results: The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones.

Conclusions: This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy.

Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008.

Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001).

Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Background: Breast cancer (BC) remains a significant global concern, particularly among developing countries in South-East Asia (SEA) and South America (SA). The socioeconomic burdens of oncologic care in those countries were often originated from limited accessibility on attainable therapeutic options and reliability on identifying essential information of cancer cells, i.e., immunohistochemical (IHC) subtyping to determine suitable approaches. The triple-negative breast cancer (TNBC) is among the most aggressive category in breast malignancy, therefore, requiring more specific molecular pathway blocking to exhaust the cells. However, large-scale epidemiological investigation on its rate among BC remains unavailable to date. This study aimed to describe the prevalence of TNBC in the SEA and SA continents since it may guide the future direction of oncologic research and trials.

Methods: This review focuses on observational studies from the SEA and SA continents from the last decade. Each study represents its country or cities, period of observation, population size, and the TNBC-BC rate as the main outcomes. Therefore, we may also limit the reporting bias originated from same-patient data on the specific occasions. The analysis will be derived to SEA-SA comparison, plus SEA/SA-specific session as processed in Comprehensive Meta-Analysis (CMA) version 3.0. The statistical analysis will be performed in random effects model (REM) within 95% confidence interval (CI).

Results: From 46 studies included in the final analysis with a total enlisted population of 34,346 unique individuals with BC, the TNBC rate was higher in the SEA compared to the SA region (19.3% vs. 15.7%; P < 0.05 in 95% CI), with the highest prevalence observed in Vietnam (22.4%) and Peru (17.8%), if it was restricted on countries with two or more studies. Interestingly, both Laos and Argentina possessed significant differences compared to other countries within their respective continents, with the highest and lowest TNBC rates (P < 0.05).

Conclusions: The IHC characteristics in SEA differ from those in the SA continent as mainly represented by TNBC prevalence, possibly shaping the course of future trials in the respective region based on IHC expressivity status.

Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will highlight the key details of the case as well as shed light on the importance of understanding the immunodeficiencies in this patient population. We highlight important aspects of the current literature related to MM and relate them to the associated case.

Background: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma constitutes a significant proportion of primary stomach lymphomas. The optimal dosage for radiotherapy and standardized follow-up protocols are yet to be universally established. This study focuses on stage I gastric MALT lymphoma patients, presenting clinical outcomes of radiotherapy with a unique dose of 30 Gy in 15 fractions and analyzing remission time.

Methods: A retrospective cohort study, approved by the institutional review board, included consecutive stage I gastric MALT lymphoma patients undergoing curative radiotherapy between 2008 and 2022. Staging followed the Lugano Modification of the Ann Arbor Staging System. The prescribed dose was uniform dose of 30 Gy in 15 fractions.

Results: Fifty-three patients were eligible, with a median age of 63 years. All achieved complete remission (CR), with a median CR time of 3.9 months. At a median follow-up of 56.8 months, no deaths occurred, and three recurrences were noted. The 5-year overall survival, local control survival, and disease-free survival rates were 100%, 100%, and 97.7%, respectively. No severe acute adverse events were observed.

Conclusion: The study demonstrates sustained and favorable long-term disease control with a 30 Gy dose in 15 fractions for stage I gastric MALT lymphoma. Comparisons with existing literature highlight the efficacy and safety of radiotherapy in achieving durable remission. Ongoing efforts explore dose reduction and technological advancements to minimize toxicity. This study emphasizes the importance of awaiting clinical response confirmation to validate these outcomes in patients with gastric MALT lymphoma.

Desmoid fibromatosis of the breast (also known as desmoid tumor of the breast) is a rare entity infrequently encountered by oncologists and surgeons caring for patients with breast disease. The current body of literature is highly reliant on case series and extrapolations from other sites of desmoid tumor-related disease. Much remains unclear regarding the pathological origins, natural history, and response to treatment of this condition. Traditional treatment strategies have centered on surgical resection, which may result in significantly disfiguring cosmetic and functional outcomes, frequent need for re-operation, and associated morbidity. There are limited data to support the superiority of upfront surgical resection when compared to medical therapy or watchful waiting strategies. Current treatment guidelines for desmoid tumors do not focus on the breast as a site of disease and are purposefully ambiguous due to the paucity of evidence available. We aim to review the literature concerning desmoid fibromatosis of the breast and propose an algorithm for current evidence-based management of this rare disease in the context of our experience with this pathology at a high-volume quaternary referral center.