OneCell Diagnostics Test provides a potent real-time monitoring system that will help in understanding the spread of cancer and the effectiveness of therapy.
Below are some of the patient case-studies:
Case Studies
Case Study 01 Colon Cancer
52 years - Female diagnosed with Signet Ring Cell Adenocarcinoma of Colon
Clinical Testing:
Alterations
Amplification
D538G
R175H
Gene
HER2
ESR1
TP53
Treatment Options
The presence of KRAS activating mutation may indicate sensitivity to MEK and BRAF inhibitors.
Indication
The patient was diagnosed with Ascending Colon (Signet Ring Cell Adenocarcinoma) Cancer and was treated with FOLFOX regimen.
Research Findings
A study including Indian colorectal cancer population reported 42.8% of activating mutations in the KRAS gene (Veldore, V H et al. 2014). The presence of these hotspot mutations leads to the constitutive activation of downstream signaling pathways resulting in uncontrolled cell proliferation. Also, these mutations are indicative of resistance to anti-EGFR inhibitors such as Cetuximab and Panitumumab
Notes
The tumor is positive for an activating mutation in the KRAS gene (G12V) which suggests recommending MEK and BRAF inhibitors.
The tumor shows loss of function in the TP53 gene, which is associated with a worse prognosis and relatively more resistant to chemotherapy and radiation.
Case Study 02Breast Cancer
48 years - Female diagnosed with left breast cancer
Clinical Testing:
Alterations
G12V
E298*
G386S
Gene
KRAS
TP53
SMAD4
Treatment Options:
The The presence of HER2 amplification suggests that HER2 inhibitors such as trastuzumab , neratinib and lapatinib can be recommended for this patient
Indication:
The patient was diagnosed with ER/PR positive and HER2 negative (by IHC) breast cancer metastasized to the bone
Research Findings:
A Literature suggests that upto 25 of the HER2 negative breast cancer patients switch to HER2 positive at metastatic recurrence around 30 of these patients have bone metastases and 50 of these bone biopsy specimens have insufficient tissue for testing in case of ESR1 gene, overall conformational changes indicate that in ESR1 MUT, there is a decreased inhibitor binding, increased coactivator recruitment, and increased proteolytic stability tha t promotes resistance to aromatase inhibitors AI), tamoxifen, and fulvestrant Merenbakh Lamin, Keren et al 2013 Brett, Jamie O et al 2021
Notes:
The tumor has an ESR1 resistance mutation (D538G) suggesting that the cancer is resistant to aromatase inhibitors, tamoxifen, and fulvestrant HER2 switch was identified from liquid biopsy which indicates recommendin g HER2 inhibitors. The tumor also shows loss of function in the TP53 gene, which is associated with a worse prognosis and relatively more resistant to chemotherapy and radiation
Case Study 03Stomach Cancer
67 years - Male diagnosed with Well-Differentiated Adenocarcinoma of Stomach
Clinical Testing:
Alterations
S285*
W129S
Gene
PALB2
PRF1
Treatment Options:
Various pre-clinical and clinical trials are evaluating the response of PARP inhibitors in gastric cancers, both as a single agent or in combination with chemotherapy or vascular angiogenic blockers (Ramucirumab). Safety / adversedrug reactions have been evaluated for Olaparib plus Paclitaxel and inOlaparib plus Cisplatin combination therapies.
Indication:
The patient was diagnosed with Well-Differentiated Adenocarcinoma ofStomach previously treated with Oxaliplatin and Leucovorin.
Research Findings:
The tumor is positive for pathogenic mutation in PALB2 and PRF1. The PALB2 gene mutation is likely of germline origin and warrants the screening of immediate family members related by blood for the inheritance of the same (which can predispose to cancers of breast, ovaries, prostate, etc). PRF1 gene mutations also have been known to predispose formative cancer cells to immune evasion and metastasis.
Case Study 04Ovarian Cancer
54 years - Female diagnosed with Recurrent Metastatic Ovarian Adenocarcinoma
Clinical Testing:
Alterations
P278T
G509R E337* Fusion
Gene
TP53
BRAF
NF1 CAD-ALK
Treatment Options:
Co-occurring mutations in BRAF and NF1 could potentially be targetable through MEK inhibitors although evidential data is lacking. Multikinase inhibitors like Pazopanib or Lenvatinib could potentially also be used in neo adjuvant settings.
Indication:
This is a heavily pre-treated case of metastatic ovarian cancer currently presenting with interval progression and bone metastases.
Research Findings:
The tumor has pathogenic mutations TP53, NF1 and BRAF genes along with a pathogenic fusion in ALK (CAD-ALK). The mutations in NF1 and TP53 are likely of germline origin and may indicate progressive disease course. The BRAF mutation (G509R also known as G469R) is classified as Class II BRAF mutation which classically does not respond to BRAF inhibitor drugs like Dabrafenib.
Case Study 05Lung Cancer
52 years - Male diagnosed with Adenocarcinoma Lung with Brain metastasis
Clinical Testing:
Alterations
P278T
G509R E337* Fusion
Gene
TP53
BRAF
NF1 CAD-ALK
Treatment Options:
Osimertinib is standard of care (NCCN) for Non-small cell lung cancer with brain metastases. Mutations in EGFR indicate potential efficacy from TKIs. MSH6 gene indicates potential benefit from Immunotherapy agents. Immunotherapy (Pembrolizumab), either as a single agent or in combination with Osimertinib has shown enhanced response and progression free survival in several studies of NSCLC with brain metastasis.
Indication:
This is the case of Adenocarcinoma Lung with symptomatic brain metastasis.
Research Findings:
The tumor has pathogenic mutations in EGFR, MSH6, TP53 and DDR2 genes. EGFR leads to increased cell proliferation and growth and is found in a variety of tumors, including non-small cell lung cancer and colorectal cancer. protein. According to AACR genie studies, MSH6 is altered in 2.44% of all cancers with colon adenocarcinoma, lung adenocarcinoma, endometrial endometrioid adenocarcinoma, breast invasive ductal carcinoma, and prostate adenocarcinoma. The tumor shows loss of function in the TP53 gene, which is associated with a worse prognosis and relatively more resistant to chemotherapy and radiation. MMR mutations (MSH6) in NSCLC are statistically correlated with resistance to Cisplatin and Carboplatin.
Case Study 06Head and Neck Cancer
54 years - Male diagnosed with Squamous cell carcinoma of Buccal Mucosa
Clinical Testing:
Alterations
G12A
I774Nfs*3 R280K Q331* R979W K722Rfs*14 R552*
Gene
HRAS
ATR
TP53 TP53 TERT RAD50 PPM1D
Treatment Options:
Overall preclinical and clinical data suggests that the use of DDR inhibitors alone or in combination with other therapies, such as radiotherapy or chemotherapy is promising, for the treatment of HNSCC (Lei, Huimin et al.2022)
Indication:
This is the case of Adenocarcinoma Lung with symptomatic brain metastasis.
Research Findings:
HRAS is altered in 3.51% of head and neck squamous cell carcinoma patients. According to COSMIC data (Oct 2022), 5.6% cases had HRAS mutations in both squamous and non-squamous carcinomas of the upper aerodigestive tract. Loss-of-function genes involved in the homologous recombination repair pathway (ATR & RAD50) can sensitize tumors to PARP inhibitors and platinum-based chemotherapy, which target the destruction of cancer cells by working in concert with HRD through synthetic lethality. Somatic missense mutations in TP53 gene implicates chemoresistance. Studies have reported that presence of promoter TERT mutations may alter the TERT levels and telomere erosion in patients with HNSCC (Boscolo-Rizzo, Paolo et al.2020)
Case Study 07Gallbladder Cancer
69 years - Male diagnosed with Adenocarcinoma-Gallbladder
Clinical Testing:
Alterations
S310F G12C S45F
Gene
ERBB2
KRAS
CTNNB1
Treatment Options:
As per the NCCN recommendations ERBB2 mutations benefit from single agent HER2 blockers (Trastuzumab) or dual HER2 blockade with Trastuzumab and Pertuzumab. KRAS G12C mutation warrants benefit from Sotorasib or even from MEK inhibitors – however efficacy of the same has not been established for Gall bladder cancers.
Indication:
This is a pre-treated case of Adenocarcinoma – Gallbladder.
Research Findings:
The tumor has pathogenic mutations in ERBB2, KRAS and CTNNB1 genes. ERBB2 (HER2) amplification and/or overexpression, and activation has been implicated in several tumor types (Moasser, M M. 2007; Lee, Jeeyun et al.2019) and are the most frequent potentially targetable alterations in GBC (14%). The presence of the KRAS gene (Veldore, V H et al. 2014) leads to the constitutive activation of downstream signaling pathways resulting in uncontrolled cell proliferation. CTNNB1 imbalance is implicated in cancer progression and metastasis (Valenta, Tomas et al.2012) and exon 3 mutations are common in endometrioid endometrial carcinoma and melanoma (Gao,Chao et al.2017).
Case Study 08Biliary Tract Cancer
68 years - Female diagnosed with Intrahepatic Cholangiocarcinoma
Clinical Testing:
Alterations
G12V K700E G386V
Gene
KRAS
SF3B1
SMAD4
Treatment Options:
MEK Inhibitor (Binimetinib) treatment can be used in this case to indirectly circumvent the impact of KRAS mutation. PD-L1 positivity is seen seen on CTCs however therapeutic responses to Immunotherapy agents have not yet been established through PD-L1 positivity on CTCs.
Indication:
This is a case of Intrahepatic Cholangiocarcinoma which was first diagnosed in Aug 2022 and was treated with chemotherapy (Gemcitabine and 5 F) in Oct–Dec 2022
Research Findings:
KRAS mutation (G12V) is a significantly poor prognosis-predictive biomarker in hepatobiliary cancers, especially when occurring in combination with SMAD4 and SF3B1 mutations. Alterations in the KRAS gene exhibit a gain of function effect. KRAS G12V is present in 3.47% of AACR GENIE cases, including pancreatic adenocarcinoma, lung adenocarcinoma, colon adenocarcinoma, colorectal adenocarcinoma, and rectal adenocarcinoma. Also SMAD4 loss/mutation was associated with poor prognosis and metastasis in intrahepatic biliary duct cancer.
Case Study 09Urothelial Carcinoma
66 years - Male diagnosed with High grade urothelial papillary carcinoma
Clinical Testing:
Alterations
Y163C P48S S9*
Gene
TP53
CDKN2A
CDH1
Treatment Options:
In general CDKN2A deficient tumors can be targeted by CDK4/6 inhibitors such as palbociclib, ribociclib and abemaciclib in different cancers, however, there are studies demonstrating reduced effect/insensitivity towards immune checkpoint inhibitors (ICI) in CDKN2A mutated tumors including urothelial cancers (Adib, Elio et al.2021;Chen, Yiyuan et al.2021). The TP53 mutation also correlates well with poor prognostic outcome and resistance to Chemotherapy undergone earlier.
Indication:
This is a case of High grade urothelial papillary carcinoma diagnosed in July 2022. The patient has progressed on the previous line of treatments - Chemotherapy & Immunotherapy.
Research Findings:
According to AACR GENIE cases, CDKN2A is altered in 22.29% and TP53 is altered in 45.06% of urothelial carcinoma patients. TP53 Somatic missense mutations are frequent in almost all cancer types (Giacomelli, Andrew O etal.2018) and are also implicated in chemoresistance (Blandino, G, et al.1999 ;Brachova, Pavla, et al.2013 ;Ferraiuolo, Maria, et al.2016). There are studies underway, indicating that abnormal TP53 alterations could be a prognostic marker in the case of urothelial cancers. CDH1 S9* results in a prematur truncation of the Cdh1 protein predicted to loss of Cdh1 expression and possible increased cell migration (Al-Ahmadie, Hikmat A et al.2016). There is an ongoing clinical trial (NCT03620643) which studies the efficacy of crizotinib in metastatic CDH1-mutated solid tumor.
Case Study 10Kidney Cancer
40 years - Female diagnosed with Renal cell carcinoma
Clinical Testing:
Alterations
F1088Sfs*2 I46Yfs*24 P129Afs*3
Gene
MSH6
BCL10
TGFBR2
Treatment Options:
The MSH6 gene mutation is indicative of Mismatch Repair deficiency and hence therapeutic response to immunotherapy(Pembrolizumab).Also, Immunotherapy markers are positive, including PDL1 on IHC.
Indication:
This is a case of Renal cell carcinoma diagnosed in the year 2018. Disease has progressed post third line of therapy.
Research Findings:
MSH6 functions in the initiation of mismatch repair systems and is associated with microsatellite instability (Cisyk, Amy L et al.2018). Loss of mutation in this gene can cause MMR deficiency and MMR deficient tumors have shown to be sensitive to PD1 inhibitors. One such inhibitor, pembrolizumab is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors.