HER2 Oncogenic mutations and amplifications are common across many Indian solid tumors
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
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.
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.
Landscape of Kinase gene fusions in cancers
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
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.
Building Genotype-Phenotype Correlation Data for Lung Cancer in India
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).
KRAS mutations in Breast cancer may be treatable
For decades, mutations in #KRAS have been known to cause cancers in multiple organs and the gene KRAS itself was considered ‘undruggable’. Of the many mutations, KRAS-G12C is known to occur in nearly 13% of #NSCLC cases. There were no known treatments that can target KRAS-G12C mutation until recently. May 2021 heralded the #fdaapproval of Sotorasib, granted to #amgen, for treatment of #lungcancer with the G12C mutation in KRAS. Exciting results showed a reduction in tumour burden in more than 37% of the trial participants. This paves the way for testing the efficacy of the drug in multiple other cancers harbouring this driver mutation. Our data identified nearly 7.8% of breast cancer #FFPE samples bearing the KRAS-G12C mutation, bringing hope of this #drug to people with #breastcancer.
1st August – World Lung Cancer Day – Focusing on Treatment for Lung Cancer
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.
showcase of Prostate cancer inventory at Sapien
Prostate cancer is the most common gender specific cancer. Prostate is the second leading site of cancer among males in large Indian cities like Delhi, Kolkata, Pune and Thiruvananthapuram, third leading site of cancer in cities like Bangalore and Mumbai. According to the Indian Council of Medical Research (ICMR) and various state cancer registries, prostate cancer is the second most common form of cancer among Indian males with an incidence rate of nine to 10 per 1,00,000 population, which is higher than Africa and other parts of Asia . Almost 75% of men diagnosed with prostatic cancer are 65 or older, but the tumors can be seen in younger adults and even in children and adolescents. Hence regular screening above the age of 60 must be done for the early signs. Early screening is the best possible way to prevent and to treat the cancer before it spreads. Screening is done by checking PSA levels, and/or MRI, Ultrasound or biopsy along with physical examination.
Targeted therapy in Gliomas based on genetic screening ?
Mutations and mutation analysis in cancer are very useful for specific #therapies that target the #mutations and spare normal cells. #precisionmedicine, especially #precisiononcology is a well-established option for #cancertreatment. With novel therapies and #therapeutics being discovered with increasing frequency, the treatment options available for combating cancers are increasingly dependent on #genomicmedicine. With adequate #cancerawareness and #cancercare along with a helping hand, defeating this deadly disease has never looked more promising.
Grade and Age distribution of Brain Cancers
glioma is a malignant cancer of the brain. Early signs include decline in brain function, memoryloss, personality changes, Vision changes etc. Based on the type of cell affected, they are classified as, Ependymoma, Astrocytoma, Oligodendroglioma, and mixed Oligoastrocytoma. Their histopathology grading is based on worldhealthorganization classification into four grades: Biologically benign gliomas WHO grade I, Low-grade gliomas WHO grade II well-differentiated and not anaplastic, and High-grade WHO grades III–IV undifferentiated or anaplastic. Sapienbio inventory has all grades of gliomas with maximum being Grade IV or glioblastoma. https://glioblastomafoundation.org/ https://www.mayoclinic.org/diseases-conditions/brain-tumor/symptoms-causes/syc-20350084 https://www.healthline.com/health/brain-tumor-charities-making-difference
May is Brain cancer awareness month
According to Global Cancer Observatory (www.gco.iarc.fr), #braincancer contributed to 2.4% of all cancers in India during 2020. They ranked 14th in the number of cases (31,460), but 10th in the number of deaths (26656) due to cancers in 2020. To tackle this deadly cancer, Sapien has collated FFPE blocks, flash frozen #tissue, live primary cells from many #braintumors to enable #drugscreening, validation of new #drugtargets and #glioma #biomarkers. We will be sharing our brain cancer research and resources through May, starting with this slide on our #FFPE blocks with matched #RWE data from 1 of our many hospitals. www.indiancancersociety.org; www.cancer.gov/types/brain;
Colorectal cancer Awareness – Choice of surgery
Colorectal cancer, also known as bowel cancer, colon cancer, or rectal cancer, is any cancer that affects the colon and the rectum. The American Cancer Society estimate that about 1 in 21 men and 1 in 23 women in the United States will develop colorectal cancer during their lifetime. It is the second leading cause of cancer death in women, and the third for men. However, due to advances in screening techniques and improvements in treatments, the death rate from colorectal cancer has been falling. Colorectal cancer may be benign, or non-cancerous, or malignant. A malignant cancer can spread to other parts of the body and damage them.
Colorectal cancer Awareness – Preventable, Treatable, Beatable
Colorectal cancer, also known as bowel cancer, colon cancer, or rectal cancer, is any cancer that affects the colon and the rectum. The American Cancer Society estimate that about 1 in 21 men and 1 in 23 women in the United States will develop colorectal cancer during their lifetime. It is the second leading cause of cancer death in women, and the third for men. However, due to advances in screening techniques and improvements in treatments, the death rate from colorectal cancer has been falling. Colorectal cancer may be benign, or non-cancerous, or malignant. A malignant cancer can spread to other parts of the body and damage them.
Recurrence in Kidney Cancer
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
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.
Types of Kidney Cancer
In India, the incidence of kidney cancer is about 2/100,000 population in males and among females, it is nearly 1/100,000 population. Renal cell carcinoma is the most common cancer type of the Kidney cancer accounting for 80 – 85 per cent. The most common sub type of RCCis Clear cell, which accounts for 75 per cent of the cases and has a better survival as compared to non – clear cell subtype (papillary & chromophobe type). The rarer subtypes are collecting duct carcinomas & renal medullary carcinomas. Oncocytoma is a slow-growing type of kidney cancer. Angiomyolipoma are the most common benign tumor but presence of epithelioid cells can lead to cancer. Renal cell carcinoma with sarcomatoid or rhabdoid features are very aggressive and have very short survival rates.
Neuroendocrine Tumors
NETs encompass a heterogeneous group of tumours arising from amine-producing Neuroendocrine cells anywhere in the body. Unlike most other cancers that start in one place, NET can occur wherever there are Neuroendocrine cells in the body. Till date the treatment therapies are not well known for NET. Because of their rarity and lack of awareness, NETs are lower priority for medical #research, but NETs are not as rare as once thought and need #personalizedmedicine since no two patients are alike.
Mutations in Lung Cancer Driving Targeted Therapy
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.
Lung Cancer Surgeries – A rare route of hope
Treatment options and recommendations for lung cancer depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health. There are 5 main ways to treat lung cancer : Surgery, Radiation therapy, Chemotherapy, Targeted therapy, Immunotherapy. The goal of surgery is to completely remove the lung tumor and the nearby lymph nodes. The following types of surgery may be used in non small cell lung cancer, aka NSCLC: Lobectomy, A wedge resection, Segmentectomy, Pneumonectomy.
Metastatic Lung Cancer-Finding cure starts with awareness
Having lung cancer or a history of lung cancer, is the cause for lung cancer metastases. Cancer that metastasizes to the lungs is a life-threatening condition that develops when cancer in another area of the body (primary organ such as breast), spreads to the lung. Prevention of metastatic lung cancer can be done by avoiding the risk factors of primary lung cancer such as smoking or chewing tobacco, or prompt and successful treatment of your primary cancer. Awareness, early detection and timely treatment are vital for preventing the spread of lung cancer.
November is a Lung cancer awareness month
The National Cancer Registry Programme Report 2020, released by the Indian Council of Medical Research (ICMR), estimates that there will be 13.9 lakh cases of cancer in India in 2020, and this number is likely to rise to 15.7 lakh by 2025. According to the data, tobacco-related PREVENTABLE cancers will account for 27.1 per cent of India’s cancer burden.
Validating herbal, natural products and drug candidates in cancer patient cells to design optimal clinical trials.
All female cancers are not PINK. Ovarian cancer is the seventh most common cancer in women worldwide. In India, it is the 3rd leading site of cancer in women. Ovarian cancer is usually diagnosed at late stages, hence disease-free and long term survival is low. This month is devoted to raising awareness for breast and ovarian cancers and get them diagnosed at an early stage to improve treatment outcomes.
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.
The Forum for Breast Cancer Protection, an NGO co-founded by caring oncologists and clinicians such as the inspiring, untiring Dr. Ramesh Sarin who continues to operate at the young age of 80 and give excellent care to her breast cancer patients. Col Pant, Dr. Sangeeta Taneja, @Karuna Sharma, Dipali Bhasin are catalysts that are active in organizing informative webinars and awareness sessions. This one on the 12th October was particularly memorable in that Ms. Sonam Kalra, a renowned singer, spoke of her mother who was diagnosed of lung cancer at the most advanced stage. She was given 6 months to live, but through her positive attitude, good routine and food, family and medical support, she lived life for 8 years, composing haikus till the end! Sonam spoke movingly of her mother and her determination to fight cancer. Her mother coined the term Cancer Samurai. Sonam sang ‘ek naam, satnam’ so beautifully it gave us goosebumps. What a treat. Then came the advice on how to use affirmation and visualization to think positively to heal our body and mind by Shivani ji, sage words in her soothing voice. Close your eyes, just listen, and feel the stress fade away.
20-30% of patients with potentially curable breast cancer develop metastasis, denying breast cancer samurais the high quality and length of life. We need to dedicate ourselves to understanding the molecular mechanism underlying Metastatic Breast Cancer which will help identify personalized screening and treatment approaches to fight metastasis
Breast cancer remains a significant societal, clinical and scientific challenge. It is very crucial to understand the epidemiology, epi/genetics, molecular pathology, cell and protein biology and the influence of hormones on its development and progression. Breast cancer remains the leading cancer in Indian women and worldwide hence raising awareness for risk factors and early detection is critical to increase the quantity and quality of life.
Lymphomas are cancers that develop in the lymphatic system. Typical symptoms start with fever, swelling of some lymph nodes, weight loss, tiredness. The affected lymph nodes could be in the neck, armpit, groin, tonsils, stomach, small intestine. Once a cancer begins in one part of the lymphatic system, it can spread rapidly to other lymph nodes so early diagnosis is important. Diagnosis is done by PET or CT scan and/or biopsy, as suggested by a doctor. The incidence of lymphomas is ~5-7% among all childhood cancers. It is 2-3 time more common in boys than in girls. In India, lymphoma was reported to be the 2nd most common cancer in young boys.
Kidney cancer rarely affects children. The most common one is Wilms’ tumor, also called nephroblastoma, that accounts for up to 95% of childhood kidney cancers, with most children being below the age of 5 years. It is a fast growing tumor that can spread (metastasize). It is usually treated by surgery, followed by radiation and chemotherapy. Commonly used chemo drugs are doxorubicin, vincristine and actinomycin D. Overall survival rates tend to be high (>90%), with favourable histopathology diagnosis and timely treatment.
India accounts for 26% of the global incidence of childhood cancers
September is Childhood Cancer Awareness Month. 30,000 children in India and 10 times that number worldwide develop cancer every year. There is a lack of awareness and timely diagnosis to treat them. Sapien will be sharing the Indian cancer data it has throughout September, starting with colorectal cancer.
Patient Samples & Data – Powering Our Products & Services
FFPE Inventory:
August is Psoriasis awareness month so highlighting Sapien’s samples, data, services for R&D
Psoriasis has a disease prevalence of 0.44-2.8 per cent in India and 2 to 3 % worldwide. There are many gaps in research to fully understand the epidemiology, aetiology, association with comorbidities, environmental variations, that all hinder optimal delivery of healthcare services in a personalized manner. There is a need for better quality data on incidence and prevalence of psoriasis to understand better the size and distribution of the problem. http://www.apps.who.int/iris/bitstream/10665/
Sapien will be able to provide – Just what you need for your Psoriasis study
Sapien provides tailor-made biosample services adhering to IRB/IEC approved specimen collection protocols, and patient informed consent forms, and coding patient information to protect privacy.
- Sample types available – Blood, tissue punch samples, other biofluids.
- Ideal patient and sample requirements – Treated or treatment naïve, type of psoriasis, collection tubes/anticoagulant, processing e.g., blood to serum or plasma, PBMCs or DNA, quantity, molecular cellular IHC assays, H&E images
- Clinical Annotation – The exact type of data needed that you need – Demographic, lifestyle, diagnostic etc.
- Storage requirements – Specimen can be stored as per your protocol or shipped as per your instructions.
Whatever your future psoriasis research needs – An image study, AI, Digital pathology, data analysis, biomarker analysis, drugs screening – we are here to help you
- Despite relatively high prevalence of psoriasis at 0.4 to 2.8 % in the Indian population and availability of many treatment options, India is behind in psoriasis disease management1.
- Research done on specific ethnic backgrounds and data from one population is not a global solution. Hence it has been recommended by WHO’s global report on Psoriasis, that Psoriasis research should focus on specific ethnicity and therapeutics that are unique to a specific population 2.
- There is an increasing demand for crucial studies addressing definitive curative therapies.
Hence, well-conducted research specific to Indian population considering the differences in genetic makeup, environmental influences and health care costs could go a long way in improving the healthcare services for the psoriasis patients 3.
- Thappa DM, Munisamy M. Research on psoriasis in India: Where do we stand? Indian J Med Res. 2017;146(2):147-149. doi: 10.4103/ijmr.IJMR_1296_17
- https://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf.psoriasis;jsessionid=54912784D28C9F36ECCD45471AC5775B?sequence=1
- Dogra S, Mahajan R. Psoriasis: Epidemiology, clinical features, co-morbidities, and clinical scoring. Indian Dermatol Online J. 2016; 7:471–80
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