34 research outputs found
Pulmonary blastoma: a comprehensive overview of a rare entity
Introduction: Pulmonary blastoma is a rare malignancy, accounting for less than 0.5% of primary lung tumors. It belongs to the group of pulmonary sarcomatoid carcinomas, and it is typically characterized by a biphasic pattern of an epithelial and a mesenchymal component. Only a few hundred cases have been reported worldwide. The aim of this study is to review and critically assess the literature regarding pulmonary blastoma.Material and methods: A narrative literature review of PubMed database from the inception of the database up to January 2021, limited to the English language, was conducted, using combinations of the following keywords: “pulmonary blastoma”, “biphasic pulmonary blastoma”, “sarcomatoid carcinoma”.Results: Pulmonary blastoma is composed of an epithelial and a mesenchymal malignant component. Regarding pathogenesis, the origin of the biphasic cell population remains elusive. Characteristic immunohistochemical stains are supportive of diagnosis.Clinically, the symptomatology is non-specific, while 40% of the cases are asymptomatic. It is diagnosed at a younger agecompared to other types of lung cancer, and it is often non-metastatic at diagnosis allowing for surgical treatment. Data on management and survival are scarce and mainly come from isolated cases. Advances on targeted therapy may provide novel treatment options. Given the rarity of the cases, multicenter collaboration is needed in order to establish therapeutic guidelines
Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations–State-of-the-Art.
Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist
Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options
The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib
Osimertinib Resistance: Molecular Mechanisms and Emerging Treatment Options
The development of tyrosine kinase inhibitors (TKIs) targeting the mutant epidermal growth factor receptor (EGFR) protein initiated the success story of targeted therapies in non-small-cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently indicated as first-line therapy in patients with NSCLC with sensitizing EGFR mutations, as second-line therapy in patients who present the resistance-associated mutation T790M after treatment with previous EGFR-TKIs, and as adjuvant therapy for patients with early stage resected NSCLC, harboring EGFR mutations. Despite durable responses in patients with advanced NSCLC, resistance to osimertinib, similar to other targeted therapies, inevitably develops. Understanding the mechanisms of resistance, including both EGFR-dependent and -independent molecular pathways, as well as their therapeutic potential, represents an unmet need in thoracic oncology. Interestingly, differential resistance mechanisms develop when osimertinib is administered in a first-line versus second-line setting, indicating the importance of selection pressure and clonal evolution of tumor cells. Standard therapeutic approaches after progression to osimertinib include other targeted therapies, when a targetable genetic alteration is detected, and cytotoxic chemotherapy with or without antiangiogenic and immunotherapeutic agents. Deciphering the when and how to use immunotherapeutic agents in EGFR-positive NSCLC is a current challenge in clinical lung cancer research. Emerging treatment options after progression to osimertinib involve combinations of different therapeutic approaches and novel EGFR-TKI inhibitors. Research should also be focused on the standardization of liquid biopsies in order to facilitate the monitoring of molecular alterations after progression to osimertinib
Immunotherapy for pancreatic cancer
Pancreatic cancer is among the most lethal malignancies resistant to
conventional therapies. The vast majority of patients is diagnosed with
advanced/metastatic disease and consequently has grim prognosis. Despite
the available options with nab-paclitaxel and gemcitabine or
5-fluorouracil/leucovorin/oxaliplatin, chemotherapy offers a modest
survival benefit. Targeted therapy in combination with chemotherapy has
not shown significant improvement in treatment outcomes. The urgent need
for new therapies has turned the spotlights on immunotherapy.
Immunotherapy in pancreatic cancer recruits and activates T cells which
recognize tumor-specific antigens.
Preclinical models have demonstrated that chemotherapy or targeted
therapy works synergistically with immunotherapy. A growing body of
evidence has already been gathered regarding the efficacy of checkpoint
inhibitors, vaccines, adoptive T cell therapy, monoclonal antibodies,
and cytokines in patients with pancreatic cancer.
Many ongoing trials are aiming to identify treatments which could
combine efficacy with limited toxicity. In this article, we review the
available data concerning multiple aspects of immunotherapy in
pancreatic cancer
Adhesion molecules in lung cancer: Implications in the pathogenesis and management
Growth and metastasis of lung cancer requires a sequence of events,
which alter the ability of neoplastic cells to adhere to themselves, to
normal surrounding cells, or to the extracellular matrix. Interactions
between cells are primarily mediated by four types of structures in the
plasma membrane: gap junctions, tight junctions, desmosomes, and
adherence junctions. We have reviewed the existing data on the
implication of adhesion molecules in the pathogenesis of lung cancer, as
well as the application of certain adhesion molecules as potential
surrogate markers in lung cancer patients
A case of trastuzumab-induced dermatomyositis
Human epidermal growth factor receptor 2 (HER-2) is a checkpoint,
controlling cell proliferation and differentiation. Trastuzumab, a
humanized monoclonal antibody directed against HER-2, is nowadays
standard treatment for breast cancer patients whose tumors express
HER-2. It is generally well tolerated, with a small number of patients
developing mild adverse reactions. Dermatomyositis is a rare adverse
event of trastuzumab therapy not well described in the literature. We
herein present a case of a patient treated for hormone-sensitive
invasive ductal carcinoma, who presented with symptoms of proximal
muscle weakness, arthralgias, skin rash, and generalized fatigue. The
symptoms started after the sixth cycle of trastuzumab and progressively
deteriorated. The patient's medical and family history was unremarkable.
Disease progression as a possible cause of dermatomyositis had been
ruled out, and laboratory evaluation revealed moderate elevation of
serum muscle proteins and acute-phase reactants. Trastuzumab treatment
was discontinued, and 3 months later, the patient was free of symptoms
without any further intervention
The Emerging Role of Tyrosine Kinase Inhibitors in Ovarian Cancer Treatment: A Systematic Review
The present systematic review summarizes current evidence regarding the
mechanisms of action, the efficacy, and the adverse effects of tyrosine
kinase inhibitors (TKIs) in ovarian cancer patients. Phase II and III
clinical trials were sought in the PubMed database and in the Clinical
Trials.gov registry through September 30, 2015. Seventy-five clinical
trials regarding TKIs targeting mainly vascular endothelial growth
factor receptor, epidermal growth factor receptor, platelet-derived
growth factor receptor, and sarcoma tyrosine kinase (Src) were yielded.
The most promising results were noted with cediranib, nintedanib, and
pazopanib. However, drawing universal conclusions about the potential
integration of TKIs in ovarian cancer therapy remains elusive.
Furthermore, emerging challenges and directions for the future research
are critically discussed
Use of Antibody–Drug Conjugates in the Early Setting of Breast Cancer
Antibody–drug conjugates (ADCs) are anticancer agents with the capacity to selectively deliver their payloads to cancer cells. Antibody–drug conjugates consist of a monoclonal antibody backbone connected by a linker to cytotoxic payloads. Antibody–drug conjugate effect occurs either by directly targeting cancer cells via membrane antigen or through “bystander effect.” Antibody–drug conjugates have demonstrated efficacy against various types of tumors, including breast cancer. Ado-trastuzumab emtansine is presently the only approved ADC for the treatment of breast cancer in the early setting, while several ADCs are now approved for metastatic breast cancer. Due to the transformative impact that several ADCs have reported in the setting of advanced breast cancer, researchers are now testing more of such compounds in the early setting, to portend benefits to patients through highly potent anticancer drugs. Ongoing trials hold the potential to transform treatment protocols for early breast cancer in the near future. These trials are aiming at evaluating different treatment modulation approaches, as informed by breast cancer risk of recurrence, including toward treatment de-escalation. Efforts are provided in ongoing clinical trials to identify the patients who will benefit most, to pursue paradigms of precision medicine with the novel ADCs. This review focuses on the potential role of ADCs in early breast cancer, providing an overview of the latest progress in their development and how they are implemented in ongoing clinical trials