HER2 Oncogenic mutations and amplifications are common across many Indian solid tumors

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Until recently, HER2 (or ErbB2) targeting drugs were only approved for HER2-amplified breast & gastric cancers. FDA has now granted accelerated approval for trastuzumab or Enhertu to treat lung cancer patients bearing activating HER2 mutations. We analyzed our data of ~1000 solid cancer cases generated using the OncomineTM Dx NGS panel to determine the pattern of ERBB2 amplification vs. mutations. We see that in some cancers, amplifications are more common (breast, gastric, endometrial cancers) but in others, activating mutations are more common (colorectal, lung, thyroid and gliomas) with the most common mutation being V842I in Indian samples. Molecular insights gained from such NGS analysis can hopefully improve precision medicine by expanding the use of approved HER2-targeting drugs for colorectal, endometrial, gliomas, thyroid and other cancer patients that are likely to benefit from them.

Digital library of whole slide Images Built at Sapien

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Sapien is focusing on the emerging area of Digital Pathology combined with Machine Learning (ML) and Artificial Intelligence (AI), to improve the diagnoses, to sub-classify patients into more clinically-relevant phenotypes and predict outcomes. Sophisticated image analysis tools combined with computational advances allow whole slide images (WSI) to be analysed using ML / AI to develop algorithms to aid pathologists and clinicians to personalize treatment.
 
For this purpose, Sapien is creating a high-resolution library of WSI from hundreds of cancer specimens’ FFPE blocks for which demographic and diagnostic data has already been curated and structured by the biobank.
In breast cancer for example, matched sets of H&E, ER, PR, HER2, Ki67/MIB images from the same case have been scanned at 40X magnification from 750+ cases, spanning all stages, grades and histotypes in pathology. Even benign breast tumors as well as normal breast tissues have been scanned as controls. Multiple scanners (Philips, Morphle, Motic) are being used to also allow normalization across different platforms for solutions.
 
ImageNet, IBM, TCGA have large image datasets in oncology; Sapien’s digital library is the largest such database for Indian cancer patients. Sapien is adding treatment and outcomes data, as well as genetic variant data, to these cancer cases, in the hope of deep learning approaches making it possible for the inexpensive, more widely available HE images to replace the need for IHC-, FISH- and gene-based biomarker analysis.
https://www.ibm.com/blogs/research/2020/03/benefits-ai-for-breast-cancer-detection/
https://www.sciencedirect.com/science/article/pii/S2153353922003510
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037318/

Dr. Jugnu Jain, CEO, delivering an invited talk on “Sustainability of Biobanking in India” at the workshop on Biobanking organized by ILBS, New Delhi.

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Quatramer’s tunability stems from the fact that the system can be modified and adjusted to deliver single or multiple ratios of payloads in order to optimize synergistic mechanisms of action in lower doses.

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Our paper is out in Frontiers in Pharmacology

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Our paper on first ever reported establishment of a cell culture from a rare brain tumor (DIG glioma), is published in Frontiers in Pharmacology journal, with Impact factor of 4.5. Such primary cultures are very useful for drugdevelopment and phenotypic screening.

https://www.frontiersin.org/articles/10.3389/fphar.2022.778193/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Pharmacology&id=778193

Sapien’s work for Hillstream BioPharma presented at AACR

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Sapien biobank evaluates novel drug candidates and formulations for global biotech and pharma companies using our proprietary panel of live cells and 3Dcellculture derived from cancer surgeries tissues. These are also called patient-derived cells or PDCs. Assays using PDCs are very valuable before going to clinical trials. We are delighted that our work done with a novel formulation in triple negative breastcancer (TNBC) proliferation and stemcell viability was included for the presentation at AACR.

Landscape of Kinase gene fusions in cancers

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Tyrosine kinases such as ALK, RET and ROS1 are often activated by translocations or chromosomal rearrangements that result in increased oncogenic activity and are attractive candidates for targeted therapy. In our #biobank, we have identified many patient samples harbouring ALK, RET and ROS1 rearrangements by NGS.

FDA approved drugs such as Crizotinib (Xalkori, #Pfizer), Ceritinib (Zykadia, #Novartis), and Alectinib (Alecensa, #Roche) that target the kinase activity of ALK; Pralsetinib (Gavreto, Roche) targeting RET fusions in NSCLC; Entrectinib (Rozlytrek, Roche) for ROS1+ metastatic NSCLCs, and novel drugs in #clinicaltrials offer promising therapeutic approaches for not just lung but also breast, colorectal and other solid tumours.

ALK targeted therapy for lung cancer: Integration of NGS genome profiling in management of ALK-mutated NSCLCs in India

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The NGS genotyping of our NSCLC cases using ThermoFisher’s Oncomine panel identified 8 genetic variants in the ALK gene in 9 cases (16.67%), some of which, such as G1202R and S1206Y surprisingly confer resistance to #Crizotinib treatment, but demonstrate sensitivity to second-generation ALK inhibitors such as #Brigatinib and #Ceritinib, which are currently approved for the treatment of metastatic lung cancers (Sullivan I et al., Ther Adv Med Oncol 2016).

Integration of NGS genetic profiling of tumour samples could play a beneficial role in the management of ALK mutated NSCLCs in India by helping identify the best targeted therapy among Brigatinib, Ceritinib and Crizotinib upfront, based on the mutational profile.

https://www.alkpositive.org/

https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/targeted-therapies.html

https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/alk-lung-cancer

Building Genotype-Phenotype Correlation Data for Lung Cancer in India

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Sapien is curating real world data for the lung cancer cases in the biobank. While 90-95% of our NSCLC samples are biopsies which are mostly exhausted in patient diagnosis and subsequent clinical #biomarker evaluation, the resection samples are being characterized genomically in Oncomine panel to correlate the demographic, diagnostic, treatment and outcomes data with genetic mutations.
The first of such 48 cases showed a very high number of SNVs (479), CNVs (5), Fusions (6) and indels (14). Highest number of mutations were observed in KEAP1 (43.2% of all mutations), followed by STK11 (31.5% of all mutations).