Showing papers in "Critical Reviews in Oncology Hematology in 2021"

Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives.

Abstract: Molecular testing has become a mandatory component of the non-small cell lung cancer (NSCLC) management. The detection of EGFR, BRAF and MET mutations as well as the analysis of ALK, ROS1, RET and NTRK translocations have already been incorporated in the NSCLC diagnostic standards, and the inhibitors of these kinases are in routine clinical use. There are emerging biomarkers, e.g., KRAS G12C substitutions and HER2 activating alterations, which are likely to enter NSCLC guidelines upon the approval of the corresponding drugs. In addition to genetic examination, NSCLCs are usually subjected to the analysis of PD-L1 protein expression in order to direct the use of immune checkpoint inhibitors. Comprehensive NSCLC testing for multiple predictive markers requires the analysis of distinct biological molecules (DNA, RNA, proteins) and, therefore, the involvement of different analytical platforms (PCR, DNA sequencing, immunohistochemistry, FISH). There are ongoing efforts aimed at the integration of multiple NSCLC molecular assays into a single diagnostic pipeline.

TMB or not TMB as a biomarker: That is the question

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the landscape of therapeutic options for many cancers. These treatments have demonstrated improved efficacy and often a more favourable toxicity profile compared to standard cytotoxic chemotherapy. There are considerable differences among responders, with some patients experiencing durable long-term disease control and even remission. Given this variability, determining a proper biomarker to select patients for ICI therapy has become increasingly important. The only biomarker proven to be predictive of overall survival benefit with ICI therapy is PD-L1 expression level measured by immunohistochemistry. Several attempts have been made to identify different predictive biomarkers. One of the most intriguing and divisive is tumor mutational burden (TMB). TMB represents the number of mutations per megabase (Mut/Mb) of DNA that were sequenced in a specific cancer. With a higher number of mutations detected, and consequentially an increase in the number neo-epitopes, then it is more likely that one or more of those neo-antigens could be immunogenic and trigger a T cell response. Initially, TMB was identified as a biomarker for ICIs in melanoma and subsequent studies suggested a possible clinical role for TMB in non-small cell lung cancer. The initial data were not confirmed in a prospective study assessing OS as the primary endpoint. Recently, the FDA has approved pembrolizumab in all cancers with a TMB > 10Mut/Mb[12] based on findings from the phase 2 KEYNOTE-158. Much criticism has emerged about this pan-cancer approval, in particular about the use of TMB as biomarker to select patients. Here we review the data about the importance and role of TMB as possible pan-cancer one-size-fits-all biomarker. We highlight the strengths and intrinsic limitations of such a complex biomarker and its adoption in the daily practice.

Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles.

Abstract: Gynecologic cancers involve the female genital organs, such as the vulva, vagina, cervix, endometrium, ovaries, and fallopian tubes. The occurrence and frequency of gynecologic cancer depends on personal lifestyle, history of exposure to viruses or carcinogens, genetics, body shape, and geographical habitat. For a long time, research into the molecular biology of cancer was broadly restricted to protein-coding genes. Recently it has been realized that non-coding RNAs (ncRNA), including long noncoding RNAs (LncRNAs), microRNAs, circular RNAs and piRNAs (PIWI-interacting RNAs), can all play a role in the regulation of cellular function within gynecological cancer. It is now known that ncRNAs are able to play dual roles, i.e. can exert both oncogenic or tumor suppressive functions in gynecological cancer. Moreover, several clinical trials are underway looking at the biomarker and therapeutic roles of ncRNAs. These efforts may provide a new horizon for the diagnosis and treatment of gynecological cancer. Herein, we summarize some of the ncRNAs that have been shown to be important in gynecological cancers.

Immune system in cancer radiotherapy: Resistance mechanisms and therapy perspectives.

Abstract: Radiotherapy is a common modality for more than half of cancer patients. Classically, radiation is known as a strategy to kill cancer cells via direct interaction with DNA or generation of free radicals. Nowadays, we know that modulation of immune system has a key role in the outcome of radiotherapy. Selecting an appropriate dose per fraction is important for stimulation of anti-tumor immunity. Unfortunately, cancer cells and other cells within tumor microenvironment (TME) promote some mechanisms implicated in the attenuation of anti-tumor immunity via exhaustion of CD8 + T lymphocytes and natural killer (NK) cells. Immunotherapy with immune checkpoint inhibitors (ICIs) has shown to be an interesting adjuvant for induction of more effective anti-tumor immunity. Clinical trial studies are ongoing for uncovering more knowledge about the efficacy of ICI combination with radiotherapy. Some newer pre-clinical studies show more effective therapeutic window for targeting PD-1 and some other targets in combination with hypofractionated radiotherapy. In this review, we explain cellular and molecular consequences in the TME following radiotherapy and promising immune targets to enhance anti-tumor immunity.

Can mHealth interventions improve quality of life of cancer patients? A systematic review and meta-analysis.

Abstract: mHealth can be used to deliver interventions to optimize Health-related quality of life (HRQoL) of cancer patients. In this systematic-review and meta-analysis, we explored the possible impact of health interventions delivered via mHealth tools on HRQoL of cancer patients. The systematic literature search was performed on July 20, 2019, to identify studies that evaluated the impact of mHealth intervention on HRQoL of cancer patients. We identified 25 studies (17 randomized controlled trials and 8 pre-post design studies; 957 patients) that evaluated mHealth interventions. The most commonly studied mHealth interventions included physical activity/ fitness interventions (9 studies), cognitive behavioral therapy (6 studies), mindfulness/ stress management (3 studies). In the majority of studies, mHealth interventions were associated with an improved HRQoL of cancer patients. The meta-analysis of the identified studies supported the positive effect of mHealth interventions for HRQoL of cancer patients. mHealth interventions are promising for improving HRQoL of cancer patients.

Breast cancer, screening and diagnostic tools: All you need to know.

Abstract: Breast cancer is one of the most frequent malignancies among women worldwide. Methods for screening and diagnosis allow health care professionals to provide personalized treatments that improve the outcome and survival. Scientists and physicians are working side-by-side to develop evidence-based guidelines and equipment to detect cancer earlier. However, the lack of comprehensive interdisciplinary information and understanding between biomedical, medical, and technology professionals makes innovation of new screening and diagnosis tools difficult. This critical review gathers, for the first time, information concerning normal breast and cancer biology, established and emerging methods for screening and diagnosis, staging and grading, molecular and genetic biomarkers. Our purpose is to address key interdisciplinary information about these methods for physicians and scientists. Only the multidisciplinary interaction and communication between scientists, health care professionals, technical experts and patients will lead to the development of better detection tools and methods for an improved screening and early diagnosis.

Chronic inflammation towards cancer incidence: A systematic review and meta-analysis of epidemiological studies.

Abstract: This systematic review and meta-analysis provides epidemiological data on the relationship between chronic inflammation, as measured by inflammatory blood parameters, and cancer incidence. Two independent researchers searched PubMed, Web Of Science and Embase databases until October 2020. In vitro studies, animal studies, studies with chronically-ill subjects or cross-sectional studies were excluded. Quality was assessed with the Newcastle-Ottawa scale. The 59 nested case-control, 6 nested case-cohort and 42 prospective cohort studies considered 119 different inflammatory markers (top three: CRP, fibrinogen and IL6) and 26 cancer types (top five: colorectal, lung, breast, overall and prostate cancer). Nineteen meta-analyses resulted in ten significant positive associations: CRP-breast (OR = 1.23[1.05-1.43];HR = 1.14[1.01-1.28)), CRP-colorectal (OR = 1.34[1.11-1.60]), CRP-lung (HR = 2.03[1.59-2.60]), fibrinogen-lung (OR = 2.56[1.86-3.54]), IL6-lung (OR = 1.41[1.12-1.78]), CRP-ovarian (OR = 1.41[1.10-1.80]), CRP-prostate (HR = 1.09[1.03-1.15]), CRP-overall (HR = 1.35[1.16-1.57]) and fibrinogen-overall (OR = 1.22[1.07-1.39]). Study quality improvements can be done by better verification of inflammatory status (more than one baseline measurement of one parameter), adjusting for important confounders and ensuring long-term follow-up.

The clinical utility of microsatellite instability in colorectal cancer.

Abstract: Microsatellite instability (MSI) became the spotlight after the US FDA' s approval of MSI as an indication of immunotherapy for cancer patients. Immunohistochemical detection of loss of MMR proteins and PCR amplification of specific microsatellite repeats are widely used in clinical practice. Next-generation sequencing is a promising tool for identifying MSI patients. Circulating tumour DNA provides a convenient alternative when tumour tissue is unavailable. MSI detection is an effective tool to screen for Lynch syndrome. Early-stage CRC patients with MSI generally have a better prognosis and a reduced response to chemotherapy; instead, they are more likely to respond to immunotherapy. In this review, we aimed to assess the clinical utility of MSI as a biomarker in CRC. We will provide an overview of the available methods for evaluation of the analytical validity of MSI detection and elaborate the evidence on the clinical validity of MSI in the management of CRC patients.

Mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection with a specific focus on lung and breast cancers: A systematic review and meta-analysis.

Abstract: Background A systematic review and meta-analysis was performed to estimate mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection. Methods A systematic search of PubMed, up to 31 January 2021, identified publications reporting the case-fatality rate (CFR) among adult patients with solid or hematological malignancies and SARS-CoV-2 infection. The CFR, defined as the rate of death in this population, was assessed with a random effect model; 95% confidence intervals (CI) were calculated. Results Among 135 selected studies (N = 33,879 patients), the CFR was 25.4% (95% CI 22.9%–28.2%). At a sensitivity analysis including studies with at least 100 patients, the CFR was 21.9% (95% CI 19.1%–25.1%). Among COVID-19 patients with lung (N = 1,135) and breast (N = 1,296) cancers, CFR were 32.4% (95% CI 26.5%–39.6%) and 14.2% (95% CI 9.3%–21.8%), respectively. Conclusions Patients with solid or hematological malignancies and SARS-CoV-2 infection have a high probability of mortality, with comparatively higher and lower CFRs in patients with lung and breast cancers, respectively.

Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: A systematic review and meta-analysis of randomized clinical trials.

Abstract: Importance Several randomized trials of neoadjuvant chemo-immunotherapy in early triple negative breast cancer (TNBC) have been recently reported, showing conflicting results. Methods We systematically searched PubMed, Cochrane CENTRAL, Embase and key oncological meetings for trials of neoadjuvant chemo-immunotherapy in TNBC. The primary endpoint was pCR, with sub-analyses based on PD-L1 expression and risk of relapse. Results Five randomized trials enrolling 1496 TNBC patients were included. We observed a statistically significant association between PD1/PD-L1 blockade addition and pCR (SOR = 1.72, 95 %CI: 1.22–2.42). The benefit was significant in the PD-L1 positive subgroup (SOR = 1.65; 95 %CI: 1.06–2.57). pCR was also significantly increased in the high-risk subgroup (SOR = 2.39; 95 %CI: 1.09–5.22), when restricting to patients receiving an anthracycline-based NACT. We found no significant association between immunotherapy addition and toxicity, and no evidence of publication bias. Conclusions The addition of PD1/PD-L1 blockade to NACT significantly improves pCR rates in TNBC patients, particularly in patients at high-risk of relapse.

Molecular landscape of recurrent cervical cancer

Abstract: Cervical cancer (CC) is a major gynecological problem in developing and underdeveloped countries. Despite the significant advancement in early detection and treatment modalities, several patients recur. Moreover, the molecular mechanisms responsible for CC recurrence remains obscure. The patients with CC recurrence often show poor prognosis and significantly high mortality rates. The clinical management of recurrent CC depends on treatment history, site, and extent of the recurrence. Owing to poor prognosis and limited treatment options, recurrent CC often presents a challenge to the clinicians. Several in vitro, in vivo, and patient studies have led to the identification of the critical molecular changes responsible for CC recurrence. Both aberrant genetic and epigenetic modifications leading to altered cell signaling pathways have been reported to impact CC recurrence. Researchers are currently trying to dissect the molecular pathways in CC and translate these findings for better management of disease. This article attempts to review the existing knowledge of disease relapse, accompanying challenges, and associated molecular players in CC.

The main sources of circulating cell-free DNA: Apoptosis, necrosis and active secretion

Abstract: Cell-free DNA (cfDNA) as an emerging biomarker with huge potential for clinical application, especially in the field of liquid biopsy. The field is now in a critical transitional period in which cfDNA-based analysis is developing rapidly. No doubt learning more about the biological knowledge of cfDNA is beneficial to catalyze this transformation process. Therefore, in this review we have summarized the characteristics of cfDNA, including its structure and origin of tissues, in order to provide researchers with a more holistic insight of cfDNA. Subsequently, we focused on the pathways that cfDNA releases from cells, such as apoptosis, necrosis, and active secretion. Additionally, the clearance of cfDNA derived from both cellular death and active secretion in the physiological environment is also discussed. Finally, we have mentioned the link between cfDNA active secretion and tumor microenvironment.

First-line systemic therapy for metastatic castration-sensitive prostate cancer: An updated systematic review with novel findings

Abstract: Although both docetaxel and androgen-receptor-axis-targeted (ARAT) agents have yielded survival improvements in combination with androgen deprivation therapy (ADT) compared to ADT alone in metastatic castration-sensitive prostate cancer (mCSPC) patients, the optimal therapeutic choice remains to be established. We analyzed estimates of the hazard ratios for death (OS-HRs) in patients treated in the first-line setting enrolled in the GETUG-AFU15, CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN trials. Overall, men with mCSPC receiving ADT with vs. without either an ARAT agent or docetaxel as first-line systemic therapy showed a pooled OS-HR of 0.69 (95 % CI: 0.61-0.78), with significant heterogeneity (p = 0.045, I2 = 52.5 %). Network meta-analysis showed an OS-HR in patients receiving an ARAT agent vs. docetaxel of 0.78 (95 %CI: 0.67-0.91). In conclusion, the evidence analysed indicates that an ARAT agent may provide improved OS outcomes compared to docetaxel. Prospective randomized trials are warranted.

Triple negative breast cancer in the era of miRNA.

Abstract: The objective of this review is to elucidate the role of miRNAs in triple negative breast cancer (TNBC). To achieve our goal, we searched databases such as PubMed, ScienceDirect, Springer, Web of Science and Scopus. We retrieved up to 1233 articles, based a rigorous selection criterion, only 197 articles were extensively reviewed. We selected articles only addressing TNBC, but not other types of breast cancer, with the employed approach being miRNA analysis and/or profiling. Our extensive review resulted in grouping of miRNAs into categories in which specific members of miRNAs have roles in specific mechanism in TNBC i.e., carcinogenesis, invasion, metastasis, apoptosis, diagnosis, prognosis, and treatment. TNBC is an aggressive subtype of breast cancer; therefore, different approaches for accurate diagnosis, prognosis and treatment are needed. In this review we summarize the up-to-date miRNA profiling, prognostic, and therapeutic findings that add to the route of controlling TNBC.

Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications

Abstract: In last years several improvements have been made in the management of prostate cancer (PCa). Androgen receptor (AR) is considered the main driver in PCa growth and progression and most drugs are directed against AR pathway. Once PCa spreads outside the prostate, androgen deprivation therapy (ADT) represents the cornerstone of treatment in hormone-sensitive prostate cancer (HSPC). Unfortunately, the response is only transient and most patients eventually develop castration-resistant prostate cancer (CRPC). Most resistance mechanisms depend on maintenance of AR signalling in castration environment. Recent discoveries of multiple growth-promoting and survival pathways in PCa suggest the importance of alternative mechanisms involved in disease progression, such as DNA damage response pathway, PTEN/PI3K/AKT/mTOR pathway, cell cycle pathway, WNT pathway, TMPRSS2/ETS fusion, neuroendocrine pattern and immune system response. In this review, we discuss the interplay between AR signaling and other molecular pathways involved in PCa pathogenesis and their therapeutic implication in advanced disease.

Immune evasion mechanisms in acute myeloid leukemia: A focus on immune checkpoint pathways.

Abstract: Immune surveillance mechanisms comprising of adaptive and innate immune systems are naturally designed to eliminate AML development. However, leukemic cells apply various immune evasion mechanisms to deviate host immune responses resulting tumor progression. One of the recently well-known immune escape mechanisms is over-expression of immune checkpoint receptors and their ligands. Introduction of blocking antibodies targeting co-inhibitory molecules achieved invaluable success in tumor targeted therapy. Moreover, several new co-inhibitory pathways are currently studying for their potential impacts on improving anti-tumor immune responses. Although immunotherapeutic strategies based on the blockade of immune checkpoint molecules have shown promising results in a number of hematological malignances, their effectiveness in AML patients showed less remarkable success. This review discusses current knowledge about the involvement of co-inhibitory signaling pathways in immune evasion mechanisms of AML and potential application of immune checkpoint inhibitors for targeted immunotherapy of this malignancy.

Introducing immunotherapy for advanced hepatocellular carcinoma patients: Too early or too fast?

Abstract: Advanced hepatocellular carcinoma (HCC) is the most frequent liver cancer. Immunotherapy has been explored in this disease in order to improve survival outcomes. Nowadays, scientific research is focusing especially on immune checkpoint inhibitors, in particular anti-PD1, anti-PD-L1 and anti-CTLA4 monoclonal antibodies (mAbs), as single-agent or in combination with other immunotherapy agents, target therapies, anti-vascular endothelial growth factor (VEGF) and other agents targeting specific molecular pathways. Other immunotherapy strategies have been assessed or are under investigation in advanced HCC, namely cytokines, adoptive cell therapy, oncolytic virus, cancer vaccines. Each treatment presents specific efficacy and toxicity profiles, strictly related to their mechanism of action and to advanced HCC tumour microenvironment (TME). The aim of this review is to outline the state-of-the-art of immunotherapy in advanced HCC treatment, highlighting data on already investigated treatment strategies, safety and toxicity (including HBV/HCV-related HCC), and ongoing clinical trials focusing on new promising therapeutic weapons.

The tumor-agnostic treatment for patients with solid tumors: a position paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIF Italian Scientific Societies.

Abstract: The personalized medicine is in a rapidly evolving scenario. The identification of actionable mutations is revolutionizing the therapeutic landscape of tumors. The morphological and histological tumor features are enriched by the extensive genomic profiling, and the first tumor-agnostic drugs have been approved regardless of tumor histology, guided by predictive and druggable genetic alterations. This new paradigm of "mutational oncology", presents a great potential to change the oncologic therapeutic scenario, but also some critical aspects need to be underlined. A process governance is mandatory to ensure the genomic testing accuracy and homogeneity, the economic sustainability, and the regulatory issues, ultimately granting the possibility of translating this model in the "real world". In this position paper, based on experts' opinion, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies revised the new agnostic biomarkers, the diagnostic technologies available, the current availability of agnostic drugs and their present indication.

Extranodal NK/T cell lymphoma, nasal type: An updated overview.

Abstract: Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is an aggressive malignancy associated with Epstein-Barr virus infection, with a geographic and racial predilection for some Asian and Latin American countries. ENKTCL-NT manifests as a necrotic process affecting nasal or upper aerodigestive structures and, rarely, extranasal sites such as skin, and the gastrointestinal tract. ENKTCL-NT was characterized by its poor prognosis irrespective of clinical stage and therapy. However, during the last two decades, advances in its clinicopathologic, genetic and molecular characterization have been achieved, as have changes in the chemotherapy regimens that, in combination with radiotherapy, are significantly improving the survival of these patients, especially in initial stages. For these reasons, we present an overview of the historical background of ENKTCL-NT along with an updated review of its potential etiological factors, clinicopathologic and molecular features, as well as its prognostic models, current treatment protocols, and future directions on potential promising therapeutic approaches.

The application of nano-medicine to overcome the challenges related to immune checkpoint blockades in cancer immunotherapy: Recent advances and opportunities.

Abstract: Although immunosurveillance mechanisms are doing their best to counteract with the development of malignant cells, immune checkpoints may serve as the "Achilles' heel" that are exploited by malignant cells. Notably, a deep understanding of this fragile site of the immune system later led to the development of immune checkpoint blockades (ICBs). At the beginning of the discovery, it seemed that these agents could push the boundaries of cancer treatment, however, their life-threatening adverse events have muted the enthusiasm into their application in cancer. It was here that nanotechnology came to the aid of ICBs, as it became evident that the combination of nano-products with ICBs guarantees the delivery of the agents into the tumor nidus, where paralyzed immune cells are waiting for healing. In the present review, we tried to illustrate a new portrait from the befitting impacts of ICBs either as single or in a combined-modal strategy with nanoparticles.

Reactive oxygen species (ROS): Critical roles in breast tumor microenvironment

Abstract: Increases in Reactive oxygen species (ROS) have been reported in breast tumors and their surrounding tumor microenvironment (TME) cells. ROS are critical factors in breast TME as they ensure bidirectional communication among various components and mediate multi-faceted roles in tumor progression and metastasis. This paper presents a detailed and comprehensive review of the studies exploring ROS and various forms of oxidative stress in cancer progression, specifically breast cancer (BC), its microenvironment and associated cell types. The paper focuses on several diverse aspects of cellular and molecular biology of cancer, with pharmacological implications of phytochemicals in BC. We also describe the role of ROS in the genetic and epigenetic reprogramming of the TME, metastasis, and drug resistance as well as regulators of BC TME. Additionally, we discuss ROS-mediated TME therapy and the therapeutic conundrum of breast TME. These contributions could prompt the development of personalized anti-cancer drugs for the treatment of highly complex and aggressive BCs.

Melanoma of unknown primary: New perspectives for an old story.

Abstract: Melanoma of unknown primary site (MUP) comprises 3-4 % of all melanomas. It mostly presents in lymph nodes (LNs), followed by subcutaneous sites, and visceral organs; nevertheless, there is a trend of increase in the relative incidence of visceral counterpart in recent years. Spontaneous regression of the primary lesion is a well-established theory, based on the evidence that melanoma can undergo regression at the primary site. MUP and stage-matched melanoma of known primary site (MKP) share similar prognostic factors. The survival rate of patients with MUP has been compared to those with stage-matched MKP. Multiple studies conducted before the era of novel therapy with immune checkpoint or BRAF/MEK inhibitors found improved survival in favor of MUP, whereas others reported equivalent or poorer outcomes. Here, we discuss the genetic and molecular features, epidemiology, diagnosis, prognostic factors, survival, and treatment of MUP in comparison with MKP, in the pre- and post-novel therapy era.

Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer

Abstract: MET receptor has emerged as a druggable target across several human cancers. Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors. Recently, capmatinib was approved for treatment of metastatic lung cancer with MET exon 14 skipping. In this review, we critically examine the current evidence on how HGF/MET combination therapies may take advantage of synergistic effects, overcome primary or acquired drug resistance, target tumor microenvironment, modulate drug metabolism or tackle pharmacokinetic issues. Preclinical and clinical studies on the combination of HGF/MET-targeted agents with conventional chemotherapeutics or molecularly targeted treatments (including EGFR, VEGFR, HER2, RAF/MEK, and PI3K/Akt targeting agents) and also the value of biomarkers are examined. Our deeper understanding of molecular mechanisms underlying successful pharmacological combinations is crucial to find the best personalized treatment regimens for cancer patients.

miR-26 family and its target genes in tumorigenesis and development

Abstract: The microRNA-26 family, including miR-26a, miR-26b, miR-1297 and miR-4465, is a group of broadly conserved small RNAs with identical sequences at the seed region. The expression of miR-26 could be induced by hypoxia via a HIF-dependent mechanism, and up-regulated during multiple cell differentiation. Accumulating studies have demonstrated that miR-26 family members could be detected in many different kinds of tumors, and their validated target genes are involved in cell metabolism, proliferation, differentiation, apoptosis, invasion and metastasis. The expression of miR-26 might be a potentially valuable biomarker and a new target for cancer therapy. In this review, miR-26 family and its target genes in tumorigenesis and development will be summarized as follows.

Efficacy and safety of PARP inhibitors in the treatment of advanced ovarian cancer: An updated systematic review and meta-analysis of randomized controlled trials.

Abstract: Background Poly-ADP-ribose polymerase (PARP) inhibitors have emerged as a novel class of therapeutics for ovarian cancer (OC); however, PARP inhibitors present a class effect adverse-event profile. Methods A comprehensive literature review was performed for phase II or III randomized controlled trials (RCTs) published up to and including January 2020. We analyzed relevant clinical trials reporting the efficacy and toxicity profile of PARP inhibitors in patients with advanced OC. We estimated hazard ratios (HRs), incidences, risk ratios (RRs) and relative 95 % confidence intervals (95 % CI) for progression-free survival (PFS) and selected adverse events, using Stata 12.0 software package. Results The systematic review process yielded 10 eligible trials comprising 4,241 patients with advanced OC for survival analysis and 4553 patients for evaluation of toxicity profile. The pooled HR (PARP inhibitor vs control group) for PFS was 0.41 (95 % CI, 0.35−0.50) in overall patients, 0.51 (95 % CI, 0.40−0.64) in unselected setting, 0.32 (95 % CI, 0.26−0.39) in BRCA mutation setting, and 0.57 (95 % CI, 0.41−0.78) in wild-type setting. Patients treated with PARP inhibitors exhibited higher risks of all-grade and high-grade haematological toxicities, including anemia, leucopenia, neutropenia, thrombocytopenia (P Conclusions This study indicated that the use of PARP inhibitor provided substantial progression-free survival (PFS) benefits, irrespective of BRCA mutation status; however, treatment with PARP inhibitor was associated with increased risks of selected treatment-related adverse events.

Comprehensive review of chromophobe renal cell carcinoma

Abstract: Chromophobe renal cell carcinoma (chRCC) is the third most common type of RCC with distinct biology compared to other kidney cancer subtypes. The heterogeneity between the RCC subtypes is associated with noticeable differences in tumor aggressiveness and risk for the development of metastatic disease. ChRCC is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations. Though the therapeutic landscape of clear cell RCC (ccRCC) has significantly evolved over the past decade, limited progress has been seen in chRCC due to its infrequent incidence. In fact, the therapeutic approach for chRCC is often extrapolated from ccRCC treatments or studies that combine several forms of nccRCC subtypes. In the new era of genetic profiling of tumors and targeted therapeutics, this review describes the epidemiology, pathology, molecular characteristics, and current management with ongoing clinical trials for chRCC.

Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review. Part 2 – Radiological features and metric markers

Abstract: After chemoradiotherapy for glioblastoma, pseudoprogression can occur and must be distinguished from true progression to correctly manage glioblastoma treatment and follow-up. Conventional treatment response assessment is evaluated via conventional MRI (contrast-enhanced T1-weighted and T2/FLAIR), which is unreliable. The emergence of advanced MRI techniques, MR spectroscopy, and PET tracers has improved pseudoprogression diagnostic accuracy. This review presents a literature review of the different imaging techniques and potential imaging biomarkers to differentiate pseudoprogression from true progression.

Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants

Abstract: The detection of germline BRCA1/2 pathogenic variant has relevant implications for the patients and their family members. Family planning, prophylactic surgery and the possibility of preimplantation genetic testing for monogenic disorders (PGT-M) to avoid transmittance of pathogenic variants to the offspring are relevant topics in this setting. PGT-M is valuable option for BRCA carriers, but it remains a controversial and underdiscussed topic. Although the advances in PGT technologies have improved pregnancy rate, there are still several important challenges associated with its use. The purpose of this review is to report the current evidence on PGT-M for BRCA1/2 carriers, ethical concerns and controversy associated with its use, reproductive implications of BRCA pathogenic variants, underlying areas in which an educational effort would be beneficial as well as possibilities for future research efforts in the field.

Exercise for individuals with bone metastases: A systematic review

Abstract: Background Exercise has the potential to improve physical function and quality of life in individuals with bone metastases but is often avoided due to safety concerns. This systematic review summarizes the safety, feasibility and efficacy of exercise in controlled trials that include individuals with bone metastases. Methods MEDLINE, Embase, Pubmed, CINAHL, PEDro and CENTRAL databases were searched up to July 16, 2020. Results A total of 17 trials were included incorporating aerobic exercise, resistance exercise or soccer interventions. Few (n = 4, 0.5%) serious adverse events were attributed to exercise participation, with none related to bone metastases. Mixed efficacy results were found, with exercise eliciting positive changes or no change. The majority of trials included an element of supervised exercise instruction (n = 16, 94%) and were delivered by qualified exercise professionals (n = 13, 76%). Conclusions Exercise appears safe and feasible for individuals with bone metastases when it includes an element of supervised exercise instruction.

A meta-analysis of CD274 (PD-L1) assessment and prognosis in colorectal cancer and its role in predicting response to anti-PD-1 therapy.

Abstract: Background PD-1 checkpoint inhibitors are novel therapeutic agents in colorectal cancer (CRC). Immunohistochemical staining for CD274 assessment is standardised in upper GI cancer, but not in CRC. Methods Methodologies of relevant studies were scrutinized and meta-analysis of survival and CD274/PDCD1 performed. Furthermore, anti-PD-1 therapy clinical trial results in CRC were assessed with particular emphasis on CD274 assessment. Results 24 studies were included. CD274 on immune cells was associated with good prognosis. CD274 on tumour cells has heterogenous outcomes and does not meet requirements of a prognostic marker. As a marker of response to anti-PD-1 therapy, CD274 assessment is not standardised in CRC. Conclusion CD274 does not appear useful as a prognostic marker. As a marker of response to anti-PD-1 therapy, assessment methodology requires standardisation. As the Combined Positive Score (CPS) is used in upper GI cancer, this seems a logical method to adopt. Thresholds for CRC remain to be determined.