Tag Archive for: targetedtherapy

Genetic Counselling an Personalized Medicine conference in Hyderabad

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Delighted to be a part of 8th Annual BGCI #conference held at the #University of Hyderabad from July 7th to 9th, 2023 where Rakesh Sharma, PhD and Madhuri R presented posters titled “Molecular landscape of #lung adenocarcinoma in India for personalizing therapy” and “Driver gene alterations in EGFR and IDH1 are mutually exclusive in Indian Gliomas”.

Jugnu Jain and Kalpana Kannabiran were invited by Dr Q. Annie Hasan to chair the session on “Psychosocial #ethical and legal issues in #genetics and #genomics ” including panelists Dhavendra kumar Mahati Chittem Saveetha Meganathan, Kelly Ormond and Peter Abad.
Reena Trivedi Vaishnavi Suresh helped put the panel together.

It was an enriching experience, filled with insightful presentations and discussions.

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/

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

1st August – World Lung Cancer Day – Focusing on Treatment for Lung Cancer

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In recognition of #WorldLungCancerDay, It is important for everyone to learn about the #riskfactors for Lung cancer along with the importance of #earlydiagnosis through #screening and timely treatment to decrease #mortality.

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.

There are 5 main treatment options : i) Surgery, ii) #Radiationtherapy, iii) #Chemotherapy, iv) Targeted therapy   v) #Immunotherapy

#Surgery includes #Lobectomy, Wedge resection, Segmentectomy, #Pneumonectomy.

#Chemotherapy is the use of #drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. It has been shown to improve both the length and quality of life for people with lung cancer of all stages. Targeted therapy is a #treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. Immunotherapy, also called biologic therapy, is designed to boost the body’s natural defenses to fight the cancer. It uses material made either by the body or in a laboratory to improve, target, or restore immune system function.

Recurrence in Kidney Cancer

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Kidney cancer most often spreads to lungs and bones, but it can also spread to brain, liver, and other organs. As it has no symptoms early on, it can spread before you even know you have it. Smoking tobacco doubles the risk of developing kidney cancer. Prevention of metastatic kidney cancer can be done by quitting smoking, maintaining a healthy body weight & eating a diet high in fruits & vegetables & low in fat. If cancer has not spread far, surgery may be a cure. If it has spread to other organs, then treatment like targeted therapy and Immunotherapy will be recommended.

 

 

Treatment for Kidney Cancer

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Kidney cancer is most often treated with Surgery, Chemotherapy, Targeted therapy, Immunotherapy, Radiation therapy or combination of these treatments. Treatment options and recommendations depend on several factors, including the cell type and stage of cancer, possible side effects and the patient’s preferences and overall health. For most kidney cancers, surgery is the initial treatment. The goal of surgery is to remove the tumor while preserving normal kidney function. The type of surgery done to remove the tumor is Radical Nephrectomy & Partial Nephrectomy.

Mutations in Lung Cancer Driving Targeted Therapy

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In recent years, personalized medicine has begun to bring new hope to people with lung cancer, especially non-small cell lung cancer. Personalized medicine involves looking at the cells obtained from a biopsy to see if there are any genetic mutations — changes in your genes — that could be linked to the type of cancer you have. Because certain chemotherapy drugs are either more or less effective than others against tumors with specific mutations, molecular analysis of your tumor, also called genomic testing, can help determine which therapies will be most likely to benefit you. The most common genetic changes that are tested for in lung cancer are in the genes EGFR, ALK, ROS, PDL 1 and KRAS.

The largest category of breast cancers are hormone receptor (HR) positive. These comprise 55-60% of all breast cancers globally as well as in India. Unlike triple negative breast cancer (TNBC), HR positive breast cancers respond well to personalized treatment with newer drugs and have a high chance of successful treatment and long-term survival even in advanced stages. Hence it is important to get them diagnosed and typed for HR positivity early on and tailor the treatment for each patient.

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