Posts

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.

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

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.

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.

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.

October is Ovarian cancer awareness month also

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.

Breast Cancer Protection,

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.