Targeting C797S mutations and beyond in non-small cell lung cancer-a mini-review.

Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases and has a high mortality worldwide, however, targeting common epidermal growth-factor receptor (EGFR) alterations (i.e., del19, L858R) has provided a paradigm shift in the treatment of NSCLC.

Use of immunoglobulin replacement therapy in patients with secondary antibody deficiency in daily practice: a European expert Q&A-based review.

Introduction: Secondary antibody deficiencies (SAD) are often a side effect of specific therapies that target B cells directly or affect the antibody response indirectly. Treatment of immunodeficiency by immunoglobulin replacement therapy (IgRT) is well established in primary antibody deficiencies, although the evidence for its use in SAD is less well established. To fill the gap and provide opinion and advice for daily practice, a group of experts met to discuss current issues and share best practical experience.

Retrospective Analysis of Treatment Pathways in Patients With BRAF-mutant Metastatic Colorectal Carcinoma - MORSE.

Background/aim: Metastatic colorectal cancer (mCRC) is a heterogeneous disease with distinct molecular subtypes. The BRAF-mutation found in approximately 8-12% of mCRC patients is associated with poor prognosis. Guideline recommendations for this population are mostly based on small cohorts due to lack of clinical data.

Impact of the changing landscape of induction therapy prior to autologous stem cell transplantation in 540 newly diagnosed myeloma patients: a retrospective real-world study.

Introduction: Autologous stem cell transplantation (ASCT) is the standard treatment for younger patients with newly diagnosed multiple myeloma (MM). However, due to restrictive exclusion criteria, more than half of eligible patients are usually excluded from transplant studies.

Methods: This retrospective monocentric analysis included 540 patients with MM who received an ASCT between 1996 and 2019.

Has programmed cell death ligand-1 an accomplice in non-small cell lung cancer?-a narrative review.

Recently approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations (e.g., capmatinib, tepotinib) are a new and important therapeutic option for the treatment of non-small cell lung cancer (NSCLC) patients harbouring c-MET alterations.

Lorlatinib in pretreated ALK- or ROS1-positive lung cancer and impact of TP53 co-mutations: results from the German early access program.

Introduction: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib.

Patients And Methods: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed.

Results: In total, 52 patients were included [median age 57 years (range 32-81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively.

Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis.

Introduction: This network meta-analysis aims to deliver an up-to-date, comprehensive efficacy and toxicity comparison of the approved first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) in order to provide support for evidence-based treatment decisions. Previous NMAs of first-line mRCC treatments either predate the approval of all the first-line TKIs currently available or do not include evaluation of safety data for all treatments.

Methods: We performed a systematic literature review and network meta-analysis of phase II/III randomised controlled trials (RCTs) assessing approved first-line TKI therapies for mRCC.

Programmed cell death ligand-1 (PD-L1) as a biomarker for non-small cell lung cancer (NSCLC) treatment-are we barking up the wrong tree?

Immunotherapy with monoclonal antibodies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) has become a standard of care treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) in first and later treatment lines with durable responses seen in approximately 10-20% of patients treated. However, the optimal selection of eligible patients who will benefit most, is far from being clear and the best biomarker has not yet been established. PD-L1 expression as a predictive biomarker for immunotherapy in NSCLC patients has shown some value for predicting response to immune checkpoint inhibitors in some studies, but not in others, and its use has been complicated by a number of factors which has prompted many researchers to establish better predictive biomarkers for immunotherapy of NSCLC.

Targeting SHP-1, 2 and SHIP Pathways: A Novel Strategy for Cancer Treatment?

Well-balanced levels of tyrosine phosphorylation, maintained by the reversible and coordinated actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), are critical for a wide range of cellular processes including growth, differentiation, metabolism, migration, and survival. Aberrant tyrosine phosphorylation, as a result of a perturbed balance between the activities of PTKs and PTPs, is linked to the pathogenesis of numerous human diseases, including cancer, suggesting that PTPs may be innovative molecular targets for cancer treatment. Two PTPs that have an important inhibitory role in haematopoietic cells are SHP-1 and SHP-2.

Targeting Developmental Pathways: The Achilles Heel of Cancer?

Developmental pathways (e.g., Notch, Hippo, Hedgehog, Wnt, and TGF-β/BMP/FGF) are networks of genes that act co-ordinately to establish the body plan, and disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer.

Second- and third-generation drugs for immuno-oncology treatment-The more the better?

Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g.

Overall survival in non-small cell lung cancer-what is clinically meaningful?

The development of molecularly targeted therapies [tyrosine kinase inhibitors (TKIs) and monoclonal antibodies] has significantly improved outcomes for patients with advanced or metastatic non-small cell lung cancer (NSCLC) resulting in improved progression-free survival (PFS), overall survival (OS) and quality of life (QoL). In addition, targeting the immune axis (CTLA-4, PD-1/PD-L1) has also shown promising results. Major goals of almost all clinical trials based on histology and molecular markers for NSCLC patients are improvements of OS and QoL.

Immunotherapies for NSCLC: Are We Cutting the Gordian Helix?

Chemotherapy is currently the standard-of-care for non-oncogene-driven advanced non-small cell lung cancer (NSCLC). Due to improvements in chemotherapeutic choices and supportive care, patients currently typically undergo multiple lines of chemotherapy as their disease progresses. Although treatments have improved over recent years, limited benefits are seen, especially in patients receiving later-line chemotherapy, as response rates can be low, response duration short and survival poor.

Improved overall survival following tyrosine kinase inhibitor treatment in advanced or metastatic non-small-cell lung cancer-the Holy Grail in cancer treatment?

Advanced or metastatic non-small-cell lung cancer (NSCLC) is characterized by a poor prognosis and few second- or third-line treatments. First-generation epidermal growth factor receptor tyrosine kinase inhibition has paved the way for targeted therapies in lung cancer. Although these drugs result in excellent responses [and significantly improved progression-free survival (PFS)] in patients with activating EGFR mutations, none of these randomized studies has yet demonstrated a statistically significant improvement of overall survival (OS).

Leukemia cutis - epidemiology, clinical presentation, and differential diagnoses.

Leukemia cutis is an extramedullary manifestation of leukemia. The frequency and age distribution depend on the leukemia subtype. The clinical and morphological findings have a wide range of cutaneous manifestations and may present with nodular lesions and plaques.