TEST:

HTG EdgeSeq Oncology Biomarker Panel (OBP)

This molecular profiling identify genes differentially expressed in teratomas that are potential biomarkers for prediction of teratoma element in postchemotherapy residues in testicular germ cell tumor patients. Moreover, inhibition of identified signaling pathways associated with GTS could represent potentially novel therapeutic targets in case of unresectable disease.

A total of 1250 ER+/HER2- BC patients (pts) with residual disease after NACT and increased risk (CPS-EG score of ≥3 or 2 with ypN+) were randomized into the PENELOPE-B (NCT01864746) trial to receive palbociclib or placebo... Classical approach of intrinsic subtyping relies on constant gene expression, limiting its scope. Adaptive subtyping can complement the classical approach, focusing on those genes that are changed during therapy. Comparison of paired samples before and after therapy is superior to classical subtyping of baseline samples.

A focused gene expression signature from FFPE kidney tumor samples can accurately predict for clinically indolent renal oncocytic tumors and for indolent ChRCC. These signatures can potentially help patients to avoid invasive procedures if applied to biopsies; and they can provide prognostic information that may provide reassurance and influence follow up if applied to tumor resections.

IHC staining confirmed the enrichment of α-smooth muscle actin-positive fibrosis in MF+ compared to MF- patients with corresponding increase of COMP-expressing stromal cells in MF+. Since COMP is associated with the known driver for fibrosis development transforming growth factor beta and with a cancer-associated fibroblasts enriched environment, it seems to be a promising new target for MF research.

In this study for the first-time revealed gene expressions associated with various CTC subpopulations. We suppose that these genes could represent potential therapeutic target aimed to inhibit metastatic cascade in breast cancer.

The increased resistance to stress is advantageous for cancer cell proliferation and chemoresistance, indicating the importance of this mutation in thyroid cancer. We are currently employing CRISPR/Cas9 to create KEAP1 knockout thyroid cancer cell lines to better understand this tumor suppressor gene on thyroid cancer.

Conclusions Single-agent IOA-244 has moderate activity in vitro in lymphoma, correlated with PI3Kδ expression. Given its favorable monotherapy safety profile, IOA-244 may be used in combination with drugs identified in the present pharmacological screen.

Design: In this cohort of 235 patients, >90% of patients were treated with Palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). Tumor evolution occurs on treatment with CDK4/6i; however, analyses of pretreatment biopsies can inform the duration of PFS. These data support discrete biological processes associated with sensitivity/resistance. Predictive algorithms could be developed to inform features of treatment decision which will require prospective validation which is ongoing.

P2; N=92; Not yet recruiting; Sponsor:MedSIR

In this study, downregulated gene expressions in appendiceal cancers are related to cell proliferation and death control mechanisms, with a trend towards overexpression of inflammatory and cell cycle pathways. It is postulated that genes involved in these pathways are hypermethylated. More research is being undertaken on epigenetics-based biomarkers for diagnosis and prognosis.

In PenelopeB, patients with HR+ breast cancer and residual disease after neoadjuvant chemotherapy (NACT) were randomized to post- neoadjuvant palbociclib versus placebo in addition to endocrine therapy... In the PenelopeB cohort of HR+ tumors, a HER2-low status in pretherapeutic core biopsies is related to improved disease-free survival, especially for those tumors that have a more aggressive intrinsic subtype. A shift of HER2-low status was observed before and after chemotherapy, indicating an adaptation of the pathway activity to therapy-induced stress, which might become relevant for future diagnostic and therapeutic approaches.

The composite predictive biomarker defined from PENELOPE-B was independently validated in a prospectively defined retrospective analysis of a subset of patients selected from PALLAS. The composite biomarker identified a subset of EBC patients deriving benefit from the addition of PAL to ET. This patient stratification approach can potentially be applied to future adjuvant clinical trials for treatment of hormone receptor–positive/HER2– EBC.

It is unclear from which lesion the 4/27 lymph nodes positive for DTC arouse. The unique molecular features of these two distinct tumors in the same patient could present challenges to disease management if the patient has persistent or recurrent disease.

Patients and In this cohort of 235 patients, >90% of patients were treated with Palbociclib in combination with either an aromatase inhibitor (AI) or fulvestrant (FUL). Tumor evolution occurs on treatment with CDK4/6 inhibitors; however, analyses of pretreatment biopsies can inform the duration of PFS. These data support discrete biological processes associated with sensitivity/resistance. Predictive algorithms could be developed to inform features of treatment decision which will require prospective validation which is ongoing.

RBsig is a prognostic biomarker in patients treated with palbociclib, suggesting it may help in patients’ risk stratification. CCNE1/RB1 is predictive of palbociclib benefit in PALOMA-3, but not in PALOMA-2 probably due to the different patient populations and characteristics. Further studies of these biomarkers in patients treated with CDK4/6 inhibitors in the metastatic as well in the adjuvant setting are warranted.

The EdgeSeq TMA data set can expand upon current biomarker data by including cancers not currently in TCGA. The primary analysis of EdgeSeq and IHC comparison suggested a unique protein-level regulation of HER3 in some tumor subtypes and highlights the importance of investigating protein levels of ADC targets in both tumor and normal tissues.

In a previous clinical trial, ISG15 expression showed predictive/prognostic value in SFT patients treated with pazopanib. The study did not achieve the prespecified conditions of the first stage of Simon and recruitment has been closed in this cohort. A combined score with PPAP2B and ISG15 expression was able to describe with different PFS groups, constituting a potential predictive score to the combination of sunitinib and nivolumab.

IMMUNOSARC (NCT03277924) is a phase Ib/II trial [from Spanish (GEIS) and Italian (ISG) sarcoma groups], that tested the combination of nivolumab (anti-PD-1 inhibitor) plus sunitinib (anti-angiogenic agent) in advanced sarcomas. Low expression of EZH2 was associated with better outcome in advanced STS patients treated with immunotherapy-based schemes. These results might support the rationale for the combination of EZH2 inhibitors with immune-modulating agents for future studies.

Our findings show that the switch from high-risk molecular subtypes (in particular LumB) to low-risk subtypes (in particular LumA) is common in neoadjuvant therapy of luminal tumors. The adaptation of luminal high-risk tumors to therapy-induced stress is crucial for the clinical outcome and the results suggest that molecular defined tumor subtypes might not be as stable as originally thought.

Methods PALOMA-2 is a double-blind, randomized study of first-line palbociclib (PAL) + letrozole (LET) for ER+/HER2- advanced BC (ABC). A standardized clinical PAM50 assay and bioinformatics approach should be used as discrepancies in gene expression platforms and algorithms lead to different results and could misguide treatment decisions. Clinical trial identification: Pfizer (NCT01740427)

"Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification."

Conclusion MamaPred test based on EdgeSeq technology represents a valuable and novel tool for a comprehensive HR+/HER2- early-stage BC characterization. A prospective validation would be necessary to demonstrate its clinical utility.

Conclusion MamaPred test based on EdgeSeq technology represents a valuable and novel tool for a comprehensive HR+/HER2- early-stage BC characterization. A prospective validation would be necessary to demonstrate its clinical utility.

Conclusion MamaPred test based on EdgeSeq technology represents a valuable and novel tool for a comprehensive HR+/HER2- early-stage BC characterization. A prospective validation would be necessary to demonstrate its clinical utility.

Conclusion MamaPred test based on EdgeSeq technology represents a valuable and novel tool for a comprehensive HR+/HER2- early-stage BC characterization. A prospective validation would be necessary to demonstrate its clinical utility.

MamaPred identifies HR+/HER2- early-stage BC patients with high-risk of distant relapse improving the prognostic value of those studies that compare MP and OT, suggesting a more precise risk classification.

PENELOPE-B did not show a benefit from the addition of 1 year palbociclib to endocrine therapy compared to placebo in the total enrolled high-risk primary breast cancer population . However, the small group of luminal-B tumors (n = 64) derived benefit from palbociclib, although without a statistically significant interaction . Further investigation is required in a larger cohort to validate a palbociclib benefit that might be confined to this group.

High tumor CCNE1 mRNA expression identified patients with relative resistance to palbociclib plus fulvestrant, validating prior observations although without statistical significance for interaction . Assessment of Cyclin E1 protein expression did not show predictive value . Investigation treatments to enhance CDK4/6 inhibitor efficacy in tumors with high CCNE1 expression is warranted.

All tissue samples of 14 neoadjuvant GM-CSF treated, 14 neoadjuvant Provenge treated, and 12 untreated prostate cancer patients were radical prostatectomy (RP) tissues, while 6 prostatitis patients and 6 non-prostatitis subjects were biopsies...These differences detected may be a result of the different panels or platforms due to their technical setting and focus. Thus, researchers should be aware of those potential differences when deciding which platform and panel to use.

ADCT-602 is an antibody drug conjugate (ADC) composed of Emab-C220, an engineered version of the anti-CD22 humanized IgG1 antibody epratuzumab, site-specifically conjugated to SG3249, which includes the DNA minor groove crosslinking pyrrolobenzodiazepine (PBD) dimer SG3199 linked to the antibody via a protease-cleavable linker (Zammarchi et al, ASH 2016). Expression signatures and other features (MZL or DHT DLBCL histology), but not the expression levels of its target, were associated with different sensitivity to the ADC. Our data supports the clinical evaluation of ADCT-602 in patients with B-cell lymphoma in addition to B-ALL.

Methods : PEARL trial is a multicenter phase 3 study that assigned 601 postmenopausal HR+/HER2- ABC pts, whose disease progressed on aromatase inhibitors (AIs), to receive PAL + ET vs capecitabine (CAPE). High expression of PLK1 is associated with intrinsic resistance to PAL and ET, this might be overcome with PLK1 inhibition.