DNA typos to blame for most Cancer Mutations

Nearly two-thirds of the mutations that drive cancers are caused by errors that occur when cells copy DNA. The findings, published in Science are the latest argument in a long-running debate over how much the environment or intrinsic factors contribute to cancer. They also suggest that many cancer mutations are not inherited and could not have been prevented by, for example, making different lifestyle choices. It’s a finding that could change how researchers wage the “war on cancer”, says study co-author Bert Vogelstein, a geneticist at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. Researchers have tended to emphasize the role of environmental factors in generating cancer mutations, he says. “If we think of the mutations as the enemies, and all the enemies are outside of our border, it’s obvious how to keep them from getting inside,” Vogelstein explains. “But if a lot of the enemies — in this case close to two-thirds — are actually inside our borders, it means we need a completely different strategy.” That strategy would emphasize early detection and treatment, in addition to prevention.

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AKT Inhibitors: A potential Cancer Immunotherapy Target

Targeted therapy is the most preferred option for cancer treatment and a number of new targets are being discovered which target cancer specific receptors, AKT being one of them. Protein kinase B (PKB), also known as AKT, belongs to serine/threonine protein kinase superfamily. AKT has been validated as a potential target as it plays a central role in many types of cancer, and studies have proven that the AKT signaling cascade is frequently impaired in many types of cancer and, in some cases; it is associated with tumor aggressiveness.

Also, AKT/PI3K pathway is an important signal transduction pathway and it has been observed that PI3K is overexpressed in ovarian and cervical cancer, along with causing mutations associated with breast cancer, glioblastoma and gastric cancer. Since AKT pathway plays a critical role in regulation of cell’s apoptotic pathway and AKT/PI3K pathway, it is being studied extensively as a target for cancer therapy.

The AKT Inhibitors pipeline has a number of drugs under development but in spite of increasing knowledge regarding AKT functions and activation, no AKT inhibitor has yet been approved for oncologic use. All the major components of the AKT pathway which consists of PI3Ks, PDK1, AKT and mTOR, are the focus of research for targeted cancer therapy, however, till now a limited number of drugs has emerged from this approach.

Midostaurin by Novartis is in pivotal stage of development for FLT3-mutated acute myeloid leukemia (AML) which has shown good results and is expected to be the first AKT Inhibitor to be approved. Major companies like Genentech, Novartis, Merck and GlaxoSmithKline are in the race for AKT inhibitors development and are expected to enter the pivotal stage soon. No approved drugs and the vast potential of AKT Inhibitors are thus the major driving factors for AKT Inhibitors pipeline.

Insight By:
Tejaswini Reddy
Associate Analyst

DelveInsight is a leading Business Consulting and Market Research Firm. We help our clients to find answers relevant to their business, facilitating their decision-making. DelveInsight also serves as a knowledge partner for business strategy and market research. We provide comprehensive analytical reports across various therapeutic indications. DelveInsight has a database of 3000+ high-quality analytical reports.

Statistical Insight on Some Common Cancers

Cancer is the leading cause of morbidity and mortality worldwide and one in every seven deaths is due to cancer. It has the worst incidence and mortality statistics. According to the International Agency for Research on Cancer (IARC), an estimated 14.1 million new cases of cancer occur with mortality of 8.2 million worldwide. There are more than 100 types of cancer. Here, in this article, statistical insight is shed on few of the major cancers viz.  lung cancer, breast cancer, colorectal cancer and prostate cancer.

  • Lung cancer is one of the wide spread cancer, World Health Organization (WHO) has reported that there were an estimated 1.8 million new cases for lung cancer in 2012 and 1.59 million estimated deaths globally. As reported by the American Cancer Society, the estimated new cases for lung cancer in 2017 would be around 222,500 and the estimated mortality would be around 155,870 in US alone. There are approximately 52 drugs approved for the treatment of Non-Small Cell Lung Cancer, showing an increased effort towards treating lung cancer.
  • Breast Cancer is also one of the most common cancers, and WHO has reported that there were estimated 1.67 million new cases in 2012 and 522,000 million estimated deaths globally. As reported by the American Cancer Society, the estimated new cases for invasive breast cancer and in situ breast cancer in 2017 would be around 252,710 and 63,410 respectively and the estimated mortality would be around 40,610 in US alone. There are approximately 63 drugs approved for the treatment of breast cancer, and a vast pipeline aiming to decrease the mortality associated with this type.
  • The statistics of WHO in terms of colorectal cancer show that globally there were around 1.36 million new cases for colorectal cancer in 2012 and 694,000 estimated deaths. As reported by the American Cancer Society, the estimated new cases in 2014 were around 136,830 and the estimated mortality was around 50,310 in US alone.
  • Prostate Cancer has also become a concern in terms of mortality and morbidity, with WHO reporting that globally there would be estimated 1.09 million new cases for prostate cancer in 2012 and 307,000 estimated deaths. The American Cancer Society also estimates new cases for colorectal cancer in 2017 to be around 161,360 and the estimated mortality to be around 26,730 in US alone. There are approximately 28 drugs approved for the treatment of prostate cancer, showing immense R&D interest.

Insight by:
Yuktie
Associate Analyst

DelveInsight is a leading Business Consulting and Market Research Firm. We help our clients to find answers relevant to their business and facilitating their decision-making. DelveInsight also serves as a knowledge partner for business strategy and market research. We provide comprehensive analytical reports across various therapeutical indications. Delveinsight has a database of 3000+ high-quality analytical reports

Most Common Cancers

Cancer, a highly morbid disease, has one of the worst incidence and mortality statistics across the globe. As reported by the American Cancer Society, the estimated annual incidence for 2016 has crossed 40,000 cases or more in USA alone. In the statistics, the most common type of cancer is breast cancer, with around 249,000 new cases in 2016 itself. Other common cancers include lung and prostate cancer. Colorectal cancers, combining colon and rectal cancers, have registered 95,270 and 39,220, new cases respectively, which amounts to a total of 134,490 new cases of colorectal cancer.

The following table gives the estimated numbers of new cases and deaths for each common cancer type:

Cancer Type Estimated New Cases Estimated Deaths
Bladder 76,960 16,390
Breast (Female – Male) 246,660 – 2,600 40,450 – 440
Colon and Rectal (Combined) 134,490 49,190
Endometrial 60,050 10,470
Kidney (Renal Cell and Renal Pelvis) Cancer 62,700 14,240
Leukemia (All Types) 60,140 24,400
Lung (Including Bronchus) 224,390 158,080
Melanoma 76,380 10,130
Non-Hodgkin Lymphoma 72,580 20,150
Pancreatic 53,070 41,780
Prostate 180,890 26,120
Thyroid 64,300 1,980
 

Source: National Cancer Institute

The Snippet: Weaponized antibodies use new tricks to fight cancer

Efforts to develop antibodies that can ferry drugs into cancer cells and minimize damage to healthy tissue are gathering steam. The next generation of these ‘weaponized antibody’ therapies, called antibody–drug conjugates (ADCs), is working its way through clinical trials. The concept that underlies these drugs is simple, as they re-purpose an antibody as a vehicle to deliver a toxic drug into a cancer cell. When the antibody in an ADC seeks out and docks onto a tumour cell, the cell takes it up and cleaves the molecular links that bind the drug to the antibody. This frees the drug to kill the cell from within. Researchers have been chasing ADCs for decades. The US Food and Drug Administration has approved three, but one was subsequently withdrawn from the market amid concerns that it was not effective and posed safety risks. The other two have met a happier fate: sales of Adcetris (brentuximab vedotin), approved in 2011 to treat lymphoma, and Kadcyla (trastuzumab emtansine), approved in 2013 to treat breast cancer, have been encouraging.

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Liquid Biopsy: Revolutionary Technique for Cancer Diagnosis

Clinicians have been conducting biopsies for a long time, for diagnosing and managing cancer, as genetic profile of tumor is analyzed through biopsy. Tissue biopsy is a traditional biopsy technique which is a time consuming and lengthy procedure, and cannot be performed routinely. Liquid Biopsy is a next generation cancer test which is an alternative to tissue biopsy. It helps in early detection of various cancers such as Breast Cancer, Ovarian Cancer, Prostate Cancer and Colon Cancer as it detects mutations in fragments of tumor DNA and tumor cells.

Liquid Biopsy is recommended for monitoring treatment response, genetic changes and resistance mechanisms in the tumor. It provides complete genetic information of genes such as Epidermal Growth Factor Receptor (EGFR) and Serine/threonine-protein kinase (BRAF) expressed on various cancer cells. It is based on Polymerase Chain Reaction (PCR) amplification or Next-Generation Sequencing (NGS) technology, and involves analysis of genetic markers such as Cell Free DNA (cfDNA) and Circulating Tumor Cells (CTCs) for tumor detection. It also detects more than two mutations that can occur in some cancers such as Melanoma and Lung Cancers, which is an advantage over tissue biopsy as the latter fails to detect two to four genetic mutations.

The process involves three step procedure including phlebotomy, separation of plasma cells from blood, isolation of cfDNA and analysis of cfDNA. It provides high positive predictive value, is safe and easy to perform and provides complete tumor genetics of a patient.

Several liquid biopsies tests have been approved. Among them, Cell Search test developed by Veridex was the first liquid biopsy screening test to be approved in China in 2012 for diagnosis of Breast Cancer. In 2015, CancerIntercept developed by Pathway Genomics was approved. Recently, Cobas EGFR Mutation Test V2 developed by Roche was approved by USFDA in 2016 for diagnosis of Non-small cell lung cancer (NSCLC). Several Companies such as San Diego, OncoCyte Corp, Myriad Genetics and Veracyte are developing liquid biopsy tests, while IIlumina, Guardant Health and Inivata are raising funding for the development of liquid biopsy tests.

Insight by: Diksha Wadhwa
Associate Analyst
DelveInsight Business Research

Cervical Cancer: Current Scenario

Cervical cancer is the second most common cause of death in women globally. Increased awareness and early diagnosis has reduced the death toll over the years; but still there is considerable risk that exists. According to the estimated of American Cancer Society, approximately 12,990 new cases of invasive cervical cancer will be diagnosed and about 4,120 women might die from cervical cancer in United States in 2016. There are many risk factors associated with the cause of cervical cancer and the most common is the persistent HPV (Human papillomavirus) infection which accounts 90% of the total cases.

Research showed that psychosocial stress is one of the crucial contributors of the prolonged infection of HPV. Women who smoke, take drugs etc. are more prone to HPV infection which further increases the chances of developing cervical cancer. Women suffering from Systemic Lupus Erythematosus (SLE) and Inflammation Bowel Syndrome (IBD) like Crohn’s disease should take extra care as they can be more likely to develop cervical cancer. Age is also an important factor. Trends indicate that occurrence of cervical cancer rises between late teens and mid 30s. Women with lowered immunity are at high risk of developing this cancer. Other factors such as multiple pregnancies, oral contraceptives, more than one sex partners etc. are more likely to contribute to the occurrence of cervical cancer.

Since cervical cancer has a large scope for treatment if detected in early stages, researchers are focusing on developing better ways of detecting precancer and cervical cancer. Prevention has always been better than cure, and in case of cancer early diagnosis increases the survival rate. Regular screening (Pap test and HPV Test) and vaccination is suggested for prevention. Cervical Cancer treatment is based on use of surgery, Chemotherapy, Radiation therapy and targeted therapy.

Several chemotherapeutics such as Cisplatin (Platinol; Bristol-Myers Squibb Company), Carboplatin (Paraplatin; Bristol-Myers Squibb Company), Paclitaxel (Taxol; Bristol-Myers Squibb), Topotecan (Hycamtin; GlaxoSmithKline), Gemcitabine (Gemzar; Eli Lilly and Company), Bevacizumab (Avastin; Genentech) are available for the treatment of advanced stages of cervical cancer. Researchers and pharmaceutical companies are focusing on targeted therapies, drugs for treating early detection, palliative care and use of biomarkers for accurate detection of cervical cancer.

Insight by
Jyoti Kumari
Associate Analyst 
DelveInsight Business Research, LLP

Notizia

Roche’s drug candidate for Multiple Sclerosis touted to be better than Merck’s Rebif

The much anticipated multiple sclerosis drug from Roche, ocrelizumab, has overtaken Merck’s Rebif according to the results of Phase III data, and has also shown great stats that could prove that it might have an edge in the hotly contested market. If the candidate is approved, Ocrevus is expected to be a tough rival, given its data in progressive MS; no other MS drug has yet proven to be effective in those hard-to-treat patients, and that success is expected to help Ocrevus in the market as well.

Risk info on cancer drugs on various websites skimpy, may give patients false hope

The researchers from the Office of Prescription Drug Promotion and RTI International analyzed 65 sites for branded cancer meds, and found out that almost all of them cited specific numbers on their effectiveness and side effects- which is not enough. It has not come as a surprise as the regulations require disclosure of effectiveness as well as side effects. The FDA agency has also found that these sites list far more treatment benefits as compared to risks, and are seriously harming the patients by providing incomplete information.

The FDA norms likely to punch a Rs 5,000 crore hole in Indian Pharma Industry

The Compliance to the US Food and Drug Administration norms might turn out to be a costly affair for Indian Pharma companies. The main reflection of this is in the way legal and professional costs have surged for many companies, more than some’s annual revenues. For 135 listed pharma companies, this has jumped threefold to Rs 5,071 crore in past five years, based on their annual reports.

Takeda sets aside $15B for U.S. M&A deals

Takeda has shown a great shift in R&D philosophy after it set aside the major part of drug research and development responsibilities and took up other development deals in oncology, vaccines and CNS. Also, it has set aside close to $15 billion for M&A deals in the USA, to buy companies that fit in with the vision Takeda has for itself.

The Snippet : HER2 Expression and its Dynamic Functional States within Circulating Breast Cancer Cells

A research published in Nature recently identified some dynamic functional states in the breast cancer cells of HER2 breast cancer. The research postulates that women who have advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, are prone to acquire a HER2-positive subpopulation after multiple courses of therapy. This acquired heterogeneity during the cancer evolution was previously unknown, and to find out the same the researchers evaluated women with ER+/HER2 primary tumours. The results show that the HER2 circulating tumour cells have shown activation of Notch and DNA damage pathways, which results in resistance to cytotoxic chemotherapy. HER2+ and HER2 circulating tumour cells are able to convert among themselves and produce daughter cells that are opposite within four cell doublings. Even though both HER2+ and HER2 tumour cells found in circulation were comparable in tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2 phenotype. Thus, these results point to some very distinct yet interconverting phenotypes present within patient population and also contributes in the progression of breast cancer and acquisition of drug resistance.

To know more, click on the link below:

http://www.nature.com/nature/journal/v537/n7618/full/nature19328.html

A promising immune stimulating target- “OX40”

For over 100 years, immunotherapy has played a significant role in the treatment of cancer. Immune stimulatory agents such as Toll-like receptor (TLR) agonists, adoptive T cell and natural killer (NK) cell therapies, cytokine-based therapies etc. have gained approval for treatment of various indications. In 1980s, receptor OX-40 was recognized and in 1990s, the cDNA for the OX40 antigen was sequenced. The ligand gained popularity once more in the 21st century as a mono as well as combination therapy for many cancers and is used in both ways now.

OX40 and its ligand OX40L, member of Tumor necrosis factor receptor superfamily, are activated on CD4 and CD8 T cells. OX40 and OX40L interaction act as co-stimulatory signals for T-cell activation. This interaction controls the absolute number of pathogenic or protective effectors T cells that are generated at the peak of the immune response. The augmentation of this interaction enhances antitumor immunity. The interaction between OX40 and OX40L also plays a central role in the development of multiple inflammatory and autoimmune diseases. This makes it fascinating therapeutic candidate for clinical application, especially in cancer and infectious disease area.

Top active companies involved in the OX40 clinical development are Genentech Inc, Pfizer and MedImmune, LLC, which are in process of developing their product candidates through different stages of development. Roche, AstraZeneca and GlaxoSmithKline have candidates, viz. MOXR0916, MEDI6383 and GSK3174998 respectively as combination agents with atezolizumab, durvalumab and pembrolizumab, respectively.

Single nucleotide polymorphisms of OX40L have been identified.  Drug candidates targeting OX-40 are used to treat various cancers. In June 2016, combination  study was examined of the PD-L1 inhibitor atezolizumab (Tecentriq) and the investigational OX40 agonist MOXR0916 which was well tolerated and showed early signs of antitumor activity in solid tumors. Thus, clinical development of OX40 agonists will help to meet unmet future needs in the field of immuno oncology.

Insight by Avita Agarwal
Associate Analyst
DelveInsight Business Research, LLP