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Examining the Microenvironment and Mutational Landscapes to Tailor Treatments

Posted on October 29, 2019 by Srivani Ravoori, PhD

In her presentation, Iyer noted that the 2D ovarian cell line models she developed were designed to capture how common driver mutations, such as TP53, BRCA1, PTEN, MYC, Cyclin E1 (CCNE1), AKT2, and KRAS, shape the interactions between cancer cells and components of the microenvironment, including immune cells. Data showed that HR-deficient and HR-proficient HGSOC tumors have distinct tumor microenvironments, and that combining an immune checkpoint inhibitor with an inhibitor of the DNA damage response protein, checkpoint kinase 1 (Chk1), produced antitumor effects and promoted cytotoxic T-cell infiltration in 2D cell lines with genes associated with HR-proficiency.

https://blog.aacr.org/ovarian-cancer-targets/?utm_medium=twitter&utm_source=social&utm_campaign=&utm_content=&sf111476637=1

Make sure to add the ,.17aspx on the link!

Also love this chart, shows all means of inhibitors under clinical evaluation and experimental!

https://ars.els-cdn.com/content/image/1-s2.0-S0163725819300208-gr1.jpg

To note this is one is for IFN to PD-L1 where SDC-1802 has been paired with CTLA-4 and FU5 chemotherapy but the PD-L1 & CTLA-4 are both Immunotherapy T-cell activation!

Here’s what google said!

“The roles of CTLA-4 and PD-1 in inhibiting immune responses, including antitumor responses, are largely distinct. CTLA-4 is thought to regulate T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T cells later in an immune response, primarily in peripheral tissues.”

And a Publication of CTLA-4 and PD-1 Pathways Similarities, Differences, and Implications of Their Inhibition.

https://journals.lww.com/amjclinicaloncology/Fulltext/2016/02000/CTLA_4_and_PD_1_Pathways__Similarities,.17.aspx

Targeting IFNa to tumor by anti-PD-L1 creates feedforward antitumor responses to overcome checkpoint blockade resistance.

https://www.nature.com/articles/s41467-018-06890-y.pdf

WHY PETROTEQ STANDS OUT FROM OTHER OIL
AND GAS PRODUCERS

https://mkt-petroteq.conversionir.com/asset/1:petroteq-report

Highlights of replacement news release!

• Production and sale of 1,000 barrels of oil, achieved in one work week of continuous operations at the Plant.

• A production rate of 200 barrels of oil per day utilizing an eight-hour work shift each day.

• A higher quality of oil on a consistent basis that meets the specifications of refiners and other buyers.

David Sealock, CEO, “The Company has been working with Valkor Engineering, a U.S. engineering firm in charge of the project, together with Alfa Laval, a leading global provider of engineering solutions, separation and fluid handling, and a centrifuge manufacturer, in improving existing processes and installing additional equipment to achieve higher production rates and to provide increase efficiencies at our Utah facility. We believe that all production issues have been resolved and the plant is now achieving continuous and stable production rates.”

https://content.equisolve.net/_147d27910cb94c9d0f92fed1c228ae21/petroteq/news/2019-10-21_UPDATE_Petroteq_Achieves_Continuous_334.pdf

Notice to Disregard News Release!

Another too follow I would have thought!

https://content.equisolve.net/_209dfd87468c9bec81aae6fcfae0a4fe/petroteq/news/2019-10-21_NOTICE_TO_DISREGARD_Petroteq_Energy_Inc__333.pdf

https://content.equisolve.net/_658ff9dcfe87483175e6b105a45028cc/petroteq/news/2019-10-21_Petroteq_Demonstrates_Stabilized_332.pdf

Don’t know yet will probably know the relationship if something is found!

Only these 2 for US patents under Byers-Lauren!

http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=0&f=S&l=50&d=PG01&Query=IN%2FByers-Lauren-%24

No assumption it is Pembrolizumab!

Krone the link you posted earlier has expired can you post again and will try and find?

Basser this one is the most meaningful publication linked to research with Byers/Sen and the one you mention Veliparib a (PARP inhibitor) with Temozolomide (Chemotherapy) in SCLC.

Full PDF Publication!

Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2018.77.7672

This one is in main media as good result beating standard care!

PARP Inhibitor and Chemotherapy!

Combination Olaparib and Temozolomide in Relapsed Small Cell Lung Cancer (SCLC)

https://cancerdiscovery.aacrjournals.org/content/early/2019/08/02/2159-8290.CD-19-0582

Hi Krone the drug Keytruda was named at the ASCO Sierra presentation slide!

Abstracts

“We further demonstrated that SRA737 potentiates the anti-tumor activity of ICB in multiple cancer models which, we believe, suggests that this combination may have potential for translational impact in several cancer types. “

“Comparison of different SRA737 treatment schedules in combination with anti-PD-(L)1 highlights the need for careful optimization of treatment dosing in order to maximize the intrinsic anti-tumor and immune-modulating activities of SRA737.”

“We further demonstrated that the combination of SRA737 with LDG shows striking activity in combination with ICB in SCLC and warrants further mechanistic”

Thanks good research Basser, here’s the link!

https://sitc.sitcancer.org/2019/abstracts/titles/index.php?filter=Checkpoint+Blockade+Therapy

Abstract P250 - Triparna Sen, PhD

Combination treatment of the oral CHK1 inhibitor, SRA737 and low dose gemcitabine, enhances the effect of PD-L1 blockade by modulating the immune microenvironment in small cell lung cancer.

RMM this is the link, but no abstracts until yet!

https://eventpilotadmin.com/web/page.php?page=Session&project=AACR19MT&id=p439

Thanks Num4 good stuff!

Will get in touch with you tomorrow! :/)

Probably about Chk1/ATR/Parp’s/wee1!

TESARO: A GSK Company?
Asli Muvaffak 12:30pm - 4:00pm Sun, Oct 27

A091 - Targeting homologous recombination repair defects in lung cancer [Board 91]

And:-?
New poster at EORTC with research that seams a good one to go with Tyk2 cancer molecule SDC-1802!

12:30pm - 4:00pm Tue, Oct 29
?Paula Chu??F. HOFFMAN-LA ROCHE LTD.

C090 - Systematic review of neurotrophic tyrosine receptor kinase inhibition as a tumor-agnostic management strategy [Board 90]

I’ve emailed Tim to see if there is a recorded version and also about long holders sentiment as I’m in the positive camp with reading research the T.Sen full Publication and others which is a real eye opener but that’s just me and remain in an isolated excitement as can be seen with the trades today and where the sp sits, I’ve asked if a service on twitter if that might help as it has done a little with other companies among other things!

How do you get to listen to the Q&A session is it recorded!