<p>Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy</p>

Drug Design Development and Therapy, Год журнала: 2020, Номер Volume 14, С. 3625 - 3649

Опубликована: Сен. 1, 2020

Abstract: PD-1/PD-L1 inhibitors are a group of immune checkpoint as front-line treatment multiple types cancer. However, the serious immune-related adverse reactions limited clinical application monoclonal antibodies, despite promising curative effects. Therefore, it is urgent to develop novel inhibitors, such small molecules, peptides or macrocycles, targeting axis meet increasing demands. Our review discussed mechanism action and presented trials currently approved targeted drugs incidence related reactions, helping clinicians pay more attention them, better formulate their intervention resolution strategies. At last, some new whose patent have been published listed, which provide development ideas judgment basis for efficacy safety inhibitors. Keywords: PD-1, PD-L1, trials, events, antibody

Язык: Английский

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Sex Differences in Cancer Immunotherapy Efficacy, Biomarkers, and Therapeutic Strategy

Molecules, Год журнала: 2019, Номер 24(18), С. 3214 - 3214

Опубликована: Сен. 4, 2019

Sex differences in innate and adaptive immune responses are known, women generally mount a stronger response than men. Cancer immunotherapy, represented by checkpoint inhibitors (ICIs), has revolutionized the treatment of cancer, sex cancer immunotherapy just starting to be revealed. Here, we summarize recent research progress concerning efficacy. On their own, ICIs tend more effective male patients compared with female patients, while combined chemotherapy patients. Male tumors usually antigenic tumors, this is reflected increased number tumor mutations germline antigens. The biomarker mutational burden (TMB), which reflects antigenicity, at predicting for lung In review, propose different therapeutic strategies sexes: For environment should enhanced, whereas antigenicity enhanced.

Язык: Английский

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Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(12), С. 4414 - 4414

Опубликована: Июнь 21, 2020

Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both tumor microenvironment (TME) at host level. review, we summarize most important immune-metabolic factors how they could be exploited therapeutically. At cellular level, increased concentration extracellular adenosine as well depletion tryptophan uncontrolled activation PI3K/AKT pathway induces immune-tolerant TME, reducing response to ICIs. Moreover, aberrant angiogenesis hypoxic environment by recruiting VEGF, Treg cells immune-suppressive associated macrophages (TAMs). On other hand, such gender body mass index seem affect ICIs, while microbiome composition (and its alterations) modulates development immune-related adverse events. Exploiting these complex mechanisms next goal immunotherapy. The successful strategy date has been combination antiangiogenic drugs which prolonged survival patients with non-small-cell lung cancer (NSCLC) hepatocellular carcinoma (HCC), results from inhibition studies are inconclusive. New exciting strategies include targeting pathway, TAMs microbiota fecal transplantation.

Язык: Английский

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Sex Differences in Differentiated Thyroid Cancer

Thyroid, Год журнала: 2021, Номер 32(3), С. 224 - 235

Опубликована: Дек. 31, 2021

Background: Sex dimorphism strongly impacts tumor biology, with most cancers having a male predominance. Uniquely, thyroid cancer (TC) is the only nonreproductive striking female predominance three- to four-fold higher incidence among females, although males generally have more aggressive disease. The molecular basis for this observation not known, and current approaches in treatment surveillance are sex specific. Summary: Although TC has overall good prognosis, 6-20% of patients develop regional or distant metastasis, one third whom responsive conventional suffer 10-year survival rate 10%. More efficacious strategies needed these TCs, as tyrosine kinase inhibitors immunotherapy major toxicities without demonstrable benefit. Emerging evidence indicates role hormones, genetics, immune system modulation both risk its progression sex-specific manner. Conclusion: Greater understanding mechanisms underlying differences pathogenesis could provide insights into development sex-specific, targeted, effective prevention, diagnosis, management. This review summarizes emerging importance pathogenesis, progression, response differentiated emphasis on system.

Язык: Английский

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The evolving landscape of sex-based differences in lung cancer: a distinct disease in women

European Respiratory Review, Год журнала: 2022, Номер 31(163), С. 210100 - 210100

Опубликована: Янв. 12, 2022

In stark contrast to a few decades ago when lung cancer was predominantly disease of men who smoke, incidence rates in women are now comparable or higher than those and rising alarmingly many parts the world. Women face unique set risk factors for compared men. These include exogenous exposures including radon, prior radiation, fumes from indoor cooking materials such as coal, addition endogenous oestrogen distinct genetic polymorphisms. Current screening guidelines only address tobacco use likely underrepresent women. were also not well represented some landmark prospective studies that led development current guidelines. diagnosed with have clear mortality benefit even other clinical demographic characteristics accounted for. However, there may be sex-based differences outcomes side effects systemic therapy, particularly chemotherapy immunotherapy. Ongoing research is needed better investigate these rapidly changing demographics worldwide.

Язык: Английский

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Lung cancer in females—sex-based differences from males in epidemiology, biology, and outcomes: a narrative review

Translational Lung Cancer Research, Год журнала: 2024, Номер 13(1), С. 163 - 178

Опубликована: Янв. 1, 2024

Background and Objective: The role of biological sex is seldom considered in characterizing lung cancer, the deadliest cancer both United States world. Lung has traditionally been regarded as a male disease; such, research female-specific phenomena frequently conflicting or absent. Currently, disparities incidence are primarily driven by females, especially non-smokers those younger age. This narrative review provides insight into sex-specific characteristics highlighting risk factors, diagnosis patterns, carcinogenesis, treatment outcomes females. Methods: PubMed database was searched on July 26, 2023 to identify published between 2013 English. Sixty-three articles were relevant, their full texts citations studied compile information for this review. Key Content Findings: Exposure-related including personal tobacco use, thought impact female more profoundly. However, studies occupational exposures underpowered conclude Data effect endogenous exogenous hormonal remain two-sided. Screening guidelines tailored white males, exacerbating race disparities. carcinogenesis immune system response not fully understood, though clearly reacts aggressively cancer. In early-stage disease, females have greater survival perioperative setting during follow-up several years, attributed favorable histopathology healthier baseline status. Sex-specific systemic continues be optimized lack standardization randomized trials makes interpreting results difficult when aggregated. Conclusions: Biological plays critical non-small cell (NSCLC), further study needed depict complex web factors that affect risk, development, outcomes. Female underrepresentation contributed understanding. As these eliminated, we can move towards effective sexes pervasive yet deadly disease.

Язык: Английский

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Immune checkpoint inhibitors-induced autoimmunity: The impact of gender

Autoimmunity Reviews, Год журнала: 2020, Номер 19(8), С. 102590 - 102590

Опубликована: Июнь 17, 2020

Язык: Английский

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The role of the sex hormone-gut microbiome axis in tumor immunotherapy

Gut Microbes, Год журнала: 2023, Номер 15(1)

Опубликована: Март 7, 2023

Accumulating evidence suggested that both gut microbiome and sex play a critical role in the efficacy of immune checkpoint blockade therapy. Considering reciprocal relationship between hormones microbiome, hormone-gut axis may participate regulation response to inhibitors (ICIs). In this review, it was attempted summarize current knowledge about influences on antitumor ICIs describe interaction microbiome. Accordingly, review discussed potential enhancing through regulating levels manipulation Collectively, provided reliable concerning tumor immunotherapy.

Язык: Английский

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An evaluation of self-perceived knowledge, attitudes and behaviours of UK oncologists about LGBTQ+ patients with cancer

ESMO Open, Год журнала: 2020, Номер 5(6), С. e000906 - e000906

Опубликована: Янв. 1, 2020

IntroductionOver one million people in the UK identify as LGBTQ+ (lesbian, gay, bisexual, transgender, queer or questioning). Research has shown that this population experience differing cancer risk factors compared with non-LGBTQ+ patients and persistent inequalities care. Literature concerning knowledge of oncologists group's healthcare needs is limited; our study aimed to evaluate knowledge, attitudes behaviours about patients.MethodsA 53-question survey was delivered via a secure online platform. Questions covered respondent demographics, majority responses on Likert scale. Oncologists were recruited email from professional bodies social media promotion. Informed consent sought fully anonymised. Multifactorial ordinal logistic regression Fisher's exact test used assess for interactions between demographics Holm-Bonferroni multiple testing correction.Results258 completed received. Respondents had median age 43 years (range 28–69); 65% consultants 35% registrars; 42% medical, 54% clinical, oncologists. 84% felt comfortable treating but only 8% agreed they confident their specific patient needs. There low rates routine enquiry sexual orientation (5%), gender identity (3%) preferred pronouns (2%). 68% should be mandatory component postgraduate training.ConclusionsThis showed feel may fail these clinic, making it more difficult meet self-awareness deficits willingness address through training. Educational resources collated developed accordance would potentially improve confidence care receive.

Язык: Английский

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Exploring the Impact of the Obesity Paradox on Lung Cancer and Other Malignancies

Cancers, Год журнала: 2022, Номер 14(6), С. 1440 - 1440

Опубликована: Март 11, 2022

There is a paradoxical relationship between obesity, as measured by BMI, and many types of cancer, including non-small-cell lung cancer. Obese cancer patients have been shown to fare better than their non-obese counterparts. To analyze the multifaceted effects obesity on oncologic outcomes, we reviewed literature paradox, methods measure adiposity, obesity-related derangements in immunology metabolism, impact confounding variables such gender, smoking, concomitant medications statins metformin. We analyzed how these aspects may contribute paradox outcomes with focus concluded that use BMI adiposity limited should be replaced method can differentiate abdominal obesity. also metabolic immunologic caused paradox. Medications, smoking are additional further research needs performed solidify mechanisms.

Язык: Английский

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