MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Dohledat

Antabus - disulfiram

  • Ucinkuje u mnoha typu Ca

Disulfiram (DSF)/copper (Cu) complex


Antiparazitika

  • Albendazol
  • Mebedazol
  • Pyrvinium
  • Ivermectin

Antiretrovirotika

  • Redukce stemness

Chemoprotective agents in case of Carboplatine and Eoposide



DNA methylation

  • The methylation of DNA is one of the most prevalent epigenetic alterations in SCLC
  • Often associated with gene silencing
  • Can result in the inactivation of various genes, including
    • Associated with immune responses, such as MHC I and II molecules

DNA methyltransferase (DNMT) selective inhibition

  • Crucial in DNA methylation

Decitabine

  • Can significantly upregulate the expression of CXCL9/CXCL10 and CCL2
    • To promote T cell and macrophage infiltration into tumor parenchyma in SCLC
  • Blockade DNA methylation with DNMT inhibitors may serve as a promising regimen
    • To modulate the TIME and improve the efficacy of immunotherapy
  • www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext

Glykosurika

  • Např. Daphagliphlozin (Forxiga)

Histone methylation

Histone methyltransferase EZH2 inhibition

  • Often overexpressed
  • Negatively related to the prognosis of patients with SCLC
  • EZH2 mediates the abnormal methylation of polycomb repressive complex 2 (PRC2)
    • Which continuously inhibits the transcription of MHC I
  • EZH2 can inhibit the expression of CXCL9/CXCL10 and CCL2
    • Thus affecting the infiltration of CD8+ T cells and macrophages

EZH2 inhibitor + with STING agonists

  • Can restore the expression of MHC I on the membrane of SCLC cells
    • Enhance T cell infiltration
    • Contributing to the improvement of immunotherapy

EPZ011989 + decitabine to inhibit of EZH2 and DNMT1

  • Increases M1-type macrophage infiltration
    • By upregulating CCL2
  • Limiting tumor growth through macrophage-mediated phagocytosis
    • In an allo-shift plant model of SCLC

Histone demethylase LSD1 inhibice

  • Wide range of transcriptional inhibition functions
  • Notably and negatively associated with MHC I in SCLC

Bomedemstat



Inhibice STAT3

  • Sníží expresi MDR1 transporteru
    • Zvýší se citlivost k chemoterapii substráty MDR1

Inhibice MYCL1, MYCN, and MYC



Innocel

  • Kyselina fytoova

Luteolin

  • Výzkum na zvířatech a v laboratoři
    • Luteolin může inhibovat růst nádorových buněk a indukovat apoptózu
    • Může také inhibovat angiogenezi
  • Studie na zvířatech
    • Luteolin může inhibovat růst nádorových buněk SCLC.
  • Luteolin inhiboval růst SCLC buněk in vitro
  • Luteolin snížil šíření SCLC buněk u myší.
  • Lidský výzkum luteolinu a SCLC
    • Některé studie naznačují, že luteolin může být bezpečný pro užívání u lidí
    • Není jasné, zda má nějaké klinické přínosy

MRP inhibice



Meformin



Melatonin



Oxygenoterapie

  • Hyperbaricka komora s kyslíkem
  • Infuzní oxygenoterapie

Pgp inhibice

  • Expression of P-gp was clearly inhibited by verapamil in all four cell lines
  • S. Following pretreatment with verapamil
    • NCI-H-446 was more sensitive to cisplatin,
    • While SPCA-1, NCI-H-460 and NCI-H-446 were more sensitive to VP-16
  • Down-regulation of P-gp
    • Is associated with intrinsic resistance to cisplatin in the NCI-H-446 and to VP-16 in SPCA-1, NCI-H-460 and NCI-H-446 cell lines.
  • Down-regulation of P-gp may be helpful for the reversion of drug resistance in some lung cancer cell line subtypes.


Schisandrin

  • Výzkum na zvířatech a v laboratoři
    • Schisandrin může inhibovat růst nádorových buněk SCLC a indukovat apoptózu
  • Schisandrin může také inhibovat angiogenezi
  • Některé studie na zvířatech
    • Schisandrin může inhibovat růst nádorových buněk SCLC
  • Schisandrin inhiboval růst SCLC buněk in vitro
  • Schisandrin snížil šíření SCLC buněk u myší.
  • Lidský výzkum schisandrinu a SCLC
    • Některé studie naznačují, že schisandrin může být bezpečný pro užívání u lidí
    • Zapotřebí dalších studií

Synergic effect with carboplatine

Synergic effect with etoposide



L-type calcium channel blockers of the dihydropyridine, phenylalkylamine and benzothiazepine classes

  • Inhibited [3H]thymidine incorporation in these cells
    • At concentrations higher than those required to block L-type channel function
  • Growth of murine Swiss 3T3 fibroblasts which do not possess L-type Ca2+ channels
    • Was inhibited by the Ca2+ channel antagonists at the same effective concentrations as in small cell lung carcinoma cells
  • Omega-conotoxin and omega-agatoxin IVA, which block the N- and P-type channel
    • Had no effect on GLC8 cell proliferation
  • The calcium channel blockers inhibited DNA synthesis
    • Most probably by a mechanism other than VDCC antagonism.
  • www.sciencedirect.com/science/article/abs/pii/092241069390202K

Poznámka:

  • Některé blokátory vápníkových kanálků by se daly používat na snížení krevního tlaku a mohly působit i na nádor
    • Je potřeba dohledat, které mají nejnadějnější profil

Cordiceps a betaglukany



Garlic and onion



Green tea



Hedgehog signaling pathway inhibition

  • Hedgehog signaling is involved in TIME remodeling in various cancers.
  • Hedgehog (HH) signaling pathway is essential for the development, maintenance, and migration of SCLC
  • Activated in 60% of SCLC
  • Blocking it significantly inhibits tumor proliferation in a mouse model of SCLC

Phase II clinical trials using HH inhibitors + chemotherapy for ES-SCLC

In mouse models

Vismodegib in breast cancer

Vismodegib or sonidegib in basal cell carcinomas

  • Inhibiting the HH pathway can also
    • Upregulate the expression of MHC I
    • Attract MHC II+, CD4+, and CD8+ T cells to infiltrate the TIME
  • Whether HH inhibitors can enhance immunotherapy in SCLC is warrants further investigation.
-www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext

WNT signaling pathway inhibition

  • Canonical Wingless/Integrated (WNT) signaling pathway
    • Conserved across various species
    • Critical role in cell proliferation, differentiation, and migration
  • Patients with recurrent SCLC
    • Mutations in the WNT signaling pathway is as high as 80% (24/30)
    • Contribute to the development of chemotherapy resistance
  • WNT/beta-catenin signaling pathway
    • Can inhibit DC recruitment in the TIME
      • Via chemokine CCL4 downregulation
        • Leading to impaired infiltration and activation of CTLs
        • Ultimately transforming hot, into cold tumors in melanoma and NSCLC with high TMB
  • SCLC is regarded as a prototypical high-TMB tumor
  • Inhibiting the WNT pathway
    • Could improve enhancing the efficacy of immunotherapy

CCL4 upregulace




Inhibice BCL2

Dichloromethane extract of U. dioica leaves (kopřiva listys)

    • IC50 concentration of 15.54 µg/mL in 48 h exposure
    • Increased expression levels of pro-apoptotic genes caspase 3 and 9
    • Reduced anti-apoptotic Bcl-2 suggested
    • Cytotoxicity was due to apoptosis induction from intrinsic (mitochondrial) pathway
  • www.mdpi.com/1420-3049/24/15/2753

Inhibice Cell cycle checkpoints and DNA damage repair pathways

  • Degree of replication stress causes SCLC tumor cells to rely heavily on cell cycle checkpoints and DNA damage repair (DDR) to ensure survival
  • Poly ADP-ribose polymerase (PARP)
    • Crucial protein involved in DDR.
    • Neither the PARP inhibitors administered as monotherapy nor a combination with other chemotherapeutic agents extended the OS of patients

Selective inhibition of DDR pathway using PARP or CHK1 inhibitors

  • Not merely upregulates PD-L1 expression in SCLC
  • Activates the STING pathway
    • Resulting in upregulation of the type I interferon genes
      • Downstream chemokines CXCL10 and CCL5
        • Inducing the infiltration of CTLs and memory T cell

Disrupting cell cycle progression in SCLC

Cyclin-dependent kinase 7 (CDK7) inhibitor YKL-5–124

  • Induces DNA replication stress and genomic instability
  • Leads to the induction of inflammation
    • Expression of pro-inflammatory cytokines and chemokines in the microenvironment
  • CDK7 inhibitor plus anti-PD-1 antibodies
    • Increases ratios of CD4+ and CD8+ T cells
    • Improve the efficacy of immunotherapy
  • Targeting cell cycle checkpoints and DDR pathways
    • May improve T cell infiltration and facilitate immunotherapy.
  • www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext

Delta-like ligand 3 (DLL3) downregulace / blokada

  • NOTCH gene family is 25% in SCLC
  • 80%+ of SCLC tumor cells abnormally overexpress the inhibitory ligand of the NOTCH pathway
    • Delta-like ligand 3 (DLL3)
    • Regulated by the transcription factor achaete-scute homolog 1 (ASCL1)
  • Continuous inhibition of NOTCH signaling
    • Is vital for maintaining the growth and neuroendocrine phenotypes of SCLC tumor cells
  • www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext


Inhibice MDR1 a MRP1

  • Zvýší nirobuněčné koncentrace etoposidu
  • Nebo překlenou nádorovou rezistenci k etoposidu danou zvýšenou expresí těchto transportérů

MYC Oncogene inhibition

  • MYC promotes tumor heterogeneity
  • Induces chemoresistance by activating NOTCH signaling
    • To transform neuroendocrine (NE) type SCLC into a non-neuroendocrine (Non-NE) type lineage
  • Transformed Non-NE SCLC express abundant APM genes
    • Generate more infiltrating CTLs
      • Associated with improved ICI effects
  • Manipulating the NOTCH pathway to eliminate tumor heterogeneity and enhance immunogenicity by upregulating APM gene
  • www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext

Integrative medicine in oncology

  • A.R.T.O.I. (Italy)

Interactions of Carboplatine and Etoposide with natural chemicals



Jod

  • Ev. radioaktivní radionuklid (po vysycení štítnice neradioaktivním jodem) před radioterapií



Kyslíková terapie

  • Barokomora
  • Intravenosní kyslíkova terapie
  • Může zesilit učinek chemoterapie na bazi oxidacniho stresu

Liposolubilní curcumin



Abnormal glucose metabolism in SCLC

  • Prominent factor affecting the TIME

SCLC heavily relies on aerobic glycolysis to produce ATP

  • Quickly exhausts limited nutrients and oxygen in the microenvironment
  • Subsequently resulting in
    • Hypoxia
    • Nutrient limitation
    • Acidic milieu
  • Confers a growth advantage on tumor cells
  • Impacts immune cell subgroups via several mechanisms

Nutrient deprivation and an acidic environment

  • Significantly reduce the cytotoxic capacity of effector immune cells
    • Depend more on glucose metabolism when activated

Lactate

  • Can also suppress
    • NK and T cell proliferation
    • Secretion of inflammatory cytokines, especially IFN-gamma

Hypoxia

  • SCLC significantly upregulates the key hypoxia-inducing factor (HIF)-1a
    • Regulates VEGF-A to promote angiogenesis
    • Upregulate lactate dehydrogenase (LDH)
      • Further accelerates glycolysis
  • Induce the chemokines CCL26 and CCL28
  • Recruit more MDSCs and Tregs
  • Release a series of growth factors and inhibitory cytokines
  • Support the growth and metastasis of tumors
  • Broadly inhibiting T-cell function

Tregs

  • Have extremely flexible metabolic characteristics
  • Can use lactate in the microenvironment
    • Taking advantage of monocarboxylate transporters (MCTs)
      • Maintain their inhibitory function

Inhibice LDH to limit the production of lactate

Inibice MCTs

  • To inhibit its transportation
    • Could be a hopeful treatment strategy for SCLC


Dyngo4a, prochlorperazine

  • Antiemetic and anti-psychotic drug
  • Dynamin inhibitor
  • Concentrates in cell membranes
  • Can bind to multiple cellular targets
  • Prochlorperazine increases the interaction between NK cells and cancer cells with a “zippering” effect
  • Blocking CME
  • Prochlorperazine blocking effect
    • By internalizing receptors, such as
      • EGFR, HGFR, VEGFR and PDGFR
    • Fast endophiline-mediated endocytosis (FEME)
    • Fast-acting tubulovesicular endocytic pathway independent from AP2 and clathrin
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC7352732/

Serotonin (5-hydroxytryptamine (5-HT))

  • Promotes the proliferation of various cancer cell types
  • Mediated through the activation of the 5-HT receptor (HTR
  • Only HTR3 is a ligand-gated ion channel
  • HTR3C was amplified with high frequency in lung cancer patients
  • HTR3C protein expression levels were significantly associated with lymph node metastasis and distant metastasis in lung cancer tissues
  • Survival analysis
    • Decrease in disease-free survival (DFS) and overall survival (OS) rates among the high-level HTR3C expression group
      • Compared with the low-level HTR3C expression group
  • HTR3C expression was a significant predictor of patient outcomes
  • HTR3C expression levels were associated with poor DFS and OS in lung cancer patients
    • HTR3C can serve as a useful predictive biomarker for lung cancer.
  • www.hindawi.com/journals/jo/2021/1901191/

Otázky

  • Stává se v průběhu nemoci serotonin rizikovým signálnem ?
  • Byla by bylokáda tohoto receptoru výhodná ?
  • Mitogenic effect of serotonin in human small cell lung carcinoma cells
    • Via both 5-HT1A and 5-HT1D receptors

Poznámka

  • Možná je hladina serotoninu fakt problémová
    • Pokud to nenastimuluje imunitu, pak to asi spíš jen podporuje růst nádoru
  • Některé nádory jsou urychleny preskripcí SSRI antidepresiv

Imunistimulace

Exprese MHC I

  • Patients with SCLC who express abundant MHC I can benefit over the long term from immunotherapy

Study 286 patients participating in the CheckMate 032

  • Expression of antigen presentation mechanism (APM) genes was associated with long-term benefits of immunotherapy for patients

72 (71%) of 102 SCLC samples expressed few or no MHC I

  • Antigen presentation protein transporter associated with antigen processing 1 (TAP1) is also universally absent in SCLC
  • Might be primarily silenced at the transcriptional level by various epigenetic modification factors, such as
    • enhancer of zeste homolog 2 (EZH2)
    • lysine-specific methylase 1 (LSD1)

Inhibiting EZH2 or LSD1 expression

  • Can significantly upregulate the expression of MHC I
    • While relieving the epigenetic suppression of TAP1,
      • Restores the MHC I antigen presentation pathway
        • Reverses resistance to immunotherapy
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Stimulace MHC II

  • Both major histocompatibility complex class II (MHC II) and MHC II-restricted CD4+ T cells
    • Play significant roles in anti-tumor immunity.
  • SCLC does not express MHC II in tumor cells
    • Has a low expression rate of only 44.1% on immune cells
      • Causing diminished CD4+ T cell activation
        • And an inferior response to immunotherapy
  • Potential of MHC II to predict immunotherapeutic effectiveness
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Stimulace class II transactivator (CIITA) exprese

  • Loss of HLA heterozygosis (LOH)
  • Deficiency in class II transactivator (CIITA) expression
    • Might be associated with MHC II dysfunction in SCLC
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

CD8+ T cells in TIME

  • Considered as key factors for successful immunotherapy of patients with SCLC
  • CD8 expression is 5.4- and 6-fold lower than that in lung adenocarcinoma and lung squamous cell carcinoma, respectively
    • SCLC is often considered an immune-cold tumor
  • Frequency and density of CTLs, which are scarce in SCLC
    • Are much higher in the stroma than in the tumor parenchyma
  • SCLC microenvironment has a common mechanism that affects CTL recruitment and infiltration
    • Profoundly affects their cytotoxic effects
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Blokáda VEGF

  • Extracellular matrix forms fine fiber intervals in the stroma of the SCLC TIME
  • Abundant vascular endothelial growth factor (VEGF) secreted by tumor and matrix cells
    • Downregulates intercellular
      • adhesion molecule 1 (ICAM-1)
      • vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells
        • Thereby reducing immune cell adhesion and transmigration
  • Blockade this process
    • Reduces neovessels
    • Increases the numbers of CD8+ T cells around normalized vessels
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Stimualce exprese CCL5 in tumor cells and CXCL9/CXCL10 in immune cells

  • Chemokines are also important factors that influence CTL infiltration
  • Co-expressing CCL5 in tumor cells and CXCL9/CXCL10 in immune cells
    • Required for CTL infiltration into the TIME in solid tumors
  • Tumor cells often reduce CCL5 expression via epigenetic silencing
  • Patients with SCLC who express abundant CCL5
    • Are more likely to have high levels of immune checkpoint expression and a hotter TIME
      • Obviously associated with longer OS (P < 0.001)
  • CCL5 might serve as a promising predictive biomarker.
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Stimualce NK buněk

Stimualce major NK cell-activating receptor ligand, natural killer group 2, member D (NKG2DL)

  • NK cells are the most critical cells
  • They can limit SCLC invasion and metastasis
  • Expression of the major NK cell-activating receptor ligand, natural killer group 2, member D (NKG2DL) in SCLC
    • Is the lowest among all tumor types
      • Due to epigenetic NKG2DL silencing at the transcriptional level

Restoring the vitality of NK cells using epigenetic drugs

  • Is a hopeful therapeutic strategy
  • NK cell activity is primarily mediated via the inflammatory cytokine IL-15

IL-15 + super-agonist N-803

  • Actives NK cells
    • Mediated successful anti-tumor effect among all molecular subtypes in vitro and in vivo
  • NK cell therapy might be more promising than T cell-based immunotherapy for tumors such as SCLC with significantly low expression of MHC molecules.
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Inhibice / apoptoza immunosupresivních buněk v tumoru

  • Various immunosuppressive cells infiltrate the SCLC TIME, including
    • regulatory T cells (Tregs)
    • tumor-associated macrophages (TAMs)
    • myeloid-derived suppressor cells (MDSCs)
  • Suppress the proliferation, activation, and infiltration of effector immune cells
    • By expressing inhibitory receptors or secreting inhibitory cytokines
      • Promoting tumor immune escape.
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Inhibice / apoptoza Tregs

  • T regs comprise the main immunosuppressive CD4+ T cell subset
  • Mediate immune suppression through
    • Secretion of:
      • TGF-beta
      • IL-10
      • IL-35
    • Upregulation of:
      • cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)
      • PD-1
      • Others
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Inhibice forkhead box P3 Treg

  • Abundant forkhead box P3 (FOXP3)+ Tregs are found in 72%+ of SCLC samples
  • T cell populations in the peripheral blood of 20 patients with limited stage (LS)-SCLC
    • 15 with ES-SCLC, eight long-term survivors, and 19 normal controls
    • More Tregs in patients with the ES-, than LS-SCLC
  • Proportion of Tregs
    • Decreased in long-term survivors
    • Increased in recurrent patients
  • Pathological tissues of 66 and 38 patients with LS-SCLC and ES-SCLC respectively
    • FOXP3 expression is associated with longer survival (P = 0.006)
  • Patients with abundant FOXP3 expression
    • Were more likely to have longer relapse-free survival (RFS) than those with low expression
      • (41 vs. 14 months, P = 0.008)
  • FOXP3 alone to characterize Treg cells in the microenvironment is imprecise
    • Underscores the heterogeneity of Treg cell subtypes
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Přesmyknutí makrofágů z M2 na M1

  • TAMs can selectively differentiate into pro-inflammatory M1 or alternative anti-inflammatory M2
    • According to different stimuli.
  • M2 TAMs account for up to 22%–45% of all immune cells in SCLC
    • TAMs mainly promote tumor progression in the TIME of SCLC
  • Tumor cells can recruit TAMs directly by secreting
    • colony stimulating factor-1(CSF-1)
    • IL-4
    • Other cytokines into the microenvironment
      • Upregulating the classical “don't eat me” signaling CD47 to evade macrophage phagocytosis
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

CD47 antibody

  • That disrupts interactions between CD47 on tumor cells and signal regulatory protein alpha (SIRPa) on macrophages in SCLC
    • Can convert TAMs into the M1 type in vivo
    • Enhance their phagocytic capacity,
    • Kill tumor cells in xenograft models through macrophage-mediated phagocytosis
      • Significantly inhibit tumor growth
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Inhibice / apoptoza MDSCs

  • Heterogeneous group of immature myeloid cells produce abundant
    • arginase 1 (ARG-1)
    • PGE2
    • inducible nitric oxide synthase (iNOS)
    • inhibitory cytokines such as IL-10 and TGF-beta
      • Which broadly suppress the function and proliferation of T and NK cells in the TIME
  • High proportion of MDSCs closely correlates with advanced staging and poor OS in SCLC
  • Targeting MDSCs to improve the SCLC TIME might be worthwhile.
    • Immunosuppressive cells such as Treg, TAM, and MSDC infiltrate extensively in the SCLC microenvironment,
    • Significantly inhibiting the anti-tumor immune response through multiple negative regulatory mechanisms

All-trans retinoic acid (ATRA)

  • Can induce MDSC differentiation into DCs macrophages in vitro and in vivo
  • Significantly enhance the immunogenicity of SCLC cancer vaccines

Gemcitabine

  • Can reduce splenic MDSC production

Gemcitabine + checkpoint kinase 1 (CHK1) inhibitor SRA737

  • Can reduce MDSCs, Tregs, M2-type TAMs, and exhausted CTLs in the SCLC microenvironment
  • Activate the STING innate immune pathway
    • To promote tumor cold-to-hot conversion
      • Enhancing the effect of PD-L1 inhibitors
  • =www.cancertreatmentreviews.com/article/S0305-7372(23)00099-3/fulltext==

Inhibice PD-L1 tumor / interakce s PD-1 T-cell

  • Tumor cells express PD-L1 and bind to the PD-1 receptor on T cells
    • Thereby facilitating the exhaustion of activated effector T cells
  • PD-L1 is usually abundantly expressed in NSCLC
    • Can predict immunotherapeutic effectiveness.
  • PD-L1 expressed in SCLC
    • Most of it occurs on the cell membrane of immune, instead of tumor cells
  • Expression of PD-L1 in almost all evaluable samples (129 of 137) was 1%-
    • 68 (49.6%) of 137 expressed PD-L1 in immune cells
  • PD-L1 positive subgroup
    • Did not have better clinical benefits than the negative subgroup
    • Confirmed in CASPIAN trial
  • Immune-coldness of the SCLC TIME, to the extent that SCLC does not rely on immune checkpoint mechanisms to exhaust CTLs
    • The later stages of the Cancer-Immunity Cycle
      • Sufficient to compete with the human immune system.

B7-H4 and B7-H6

  • Associated with effector immune cell anti-tumor effects in SCLC

Blokáda / downregulace TIGIT

  • TIGIT is a receptor that localizes on the surfaces of T and NK cells
  • Primarily mediates immune suppression
    • By binding to high affinity to CD155 on the tumor cell
  • Abundant TIGIT/CD155 expression in SCLC
    • Significantly correlates with shorter survival
  • TIGIT can inhibit immune cells at several steps of the tumor immune cycle - inhibits:
    • DC antigen presentation
    • Co-stimulatory signals to T cells like CTLA-4/B7
    • Induces the anti-inflammatory cytokine IL-10
      • To reduce T cell activation
    • Directly the tumor-killing effect of CD8+ T and NK cells to mediate immune escape

Inhibitors of TIGIT + PD-1/PD-L1 inhibitors

  • Confer synergistic complementary effects,
  • Promoting the proliferation and function of CD8+ T cells in vitro
  • Enhancing anti-tumor effects in mouse tumor models

Phase II CITYSCAPE-02 trial

  • Improved overall response rates (ORRs) and the progression-free survival (PFS) of patients with NSCLC
    • By adding the TIGIT inhibitor tiragolumab to atezolizumab and chemotherapy

Phase III SKYSCRAPER-02 trial atezolizumab + etoposide/cisplatin + tiragolumab / placebo

  • As first-line treatment for 490 patients with ES-SCLC
  • Interim results did not reach the co-primary endpoint of PFS improvement
  • Other co-primary endpoint of OS is unlikely to reach statistical significance in the planned final analysis

Inhibice / downregulace co-inhibitory receptor for T cells, B7-H3

  • B7-H3 overexpressed in various solid tumors
  • Detection rate is 64.9% in SCLC,
  • Barely expressed in normal tissues
  • B7-H3 has recently become an emerging target

Antibody-drug conjugate (ADC) DS-7300

  • Targets B7-H3

Phase I and II trials (NCT04145622)

  • With an ORR of 11 (58%) of 19 in SCLC patients
  • Suggesting B7-H3 may serve as a potential target for the treatment of SCLC
  • SCLC patients with high B7-H6 expression
    • Had a significantly prolonged PFS (P = 0.037)
    • Significantly increased immune cell infiltration
    • Reduced NK cell activation,
      • Indicating a complicated interaction between B7-H6 and the SCLC TIME
  • B7 family of co-signaling molecules that play key roles in T cell activation
    • Is closely correlated with anti-tumor immunity in SCLC.
  • Expression of the B7 family in SCLC immune cells remains unclear

ADC drugs

  • Target B7-H3
  • Have shown a significantly higher ORR in early clinical studies


Selen: Selen je minerál, který má protizánětlivé a antioxidační účinky. Studie naznačují, že selen může pomoci snížit riziko vzniku rakoviny plic a také pomoci při léčbě tohoto onemocnění.Vitamin D: Vitamin D má protizánětlivé a antioxidační účinky. Studie naznačují, že vitamin D může pomoci snížit riziko vzniku rakoviny plic.Vitamin E: Vitamin E má antioxidační účinky. Studie naznačují, že vitamin E může pomoci snížit riziko vzniku rakoviny plic.L-karnitin: L-karnitin je aminokyselina, která má protizánětlivé a antioxidační účinky. Studie naznačují, že L-karnitin může pomoci snížit riziko vzniku rakoviny plic.Artemisinin: Artemisinin je látka, která se vyskytuje v rostlině Artemisia annua. Studie naznačují, že artemisinin může mít protinádorové účinky.Je důležité poznamenat, že žádná z těchto potravin nebo surovin nemůže sám o sobě zabránit nebo vyléčit rakovinu plic. Nicméně mohou být součástí celkového přístupu k léčbě rakoviny plic.

O úroveň výše

Poslední aktualizace: 10. 12. 2023 2:01:14