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Attacking Cancer Cells That Develop Resistance

Cancer remains one of the most intimating challenges in modern medicine, affecting millions of lives worldwide. While cancer treatment progress has been significant, resistance to therapies remains a serious challenge. Cancer cells often adapt and develop resistance to treatments that were once effective, leading to treatment failure and disease progression.

This article explores resistant cancer cells and current strategies to overcome them. Understanding resistance mechanisms and using advanced treatments can ensure successful treatment outcomes despite resistance challenges.

Understanding Cancer Cell Resistance

Cancer treatment faces a significant challenge: cancer cells become resistant to therapies that once worked. These resistance mechanisms vary from genetic mutations and epigenetic changes within cancer cells to the influence of the tumor microenvironment.

The consequences of untreated or recurrent cancer due to resistance are dire, often leading to poor outcomes and decreased quality of life for patients. Despite advancements in our understanding of these mechanisms, overcoming resistance remains a daunting task. The situation demands a collective effort to address this issue head-on.

Moreover, the economic burden of ineffective treatments adds another layer of urgency to the search for solutions. To combat this, it’s crucial to understand these mechanisms and find ways to target resistant cancer cells effectively.

Mechanisms of Resistance

  1. Genetic Mutations: Cancer cells can develop genetic mutations over time, making them less responsive to treatment. These mutations affect important cell functions, allowing cancer cells to survive and grow despite treatment.
  2. Epigenetic Changes: Changes in gene activity, called epigenetic alterations, also contribute to resistance. These changes can silence genes that control cancer growth or activate genes that promote it, making treatment less effective.
  3. Tumor Microenvironment: The environment around tumors plays a role too. Factors like low oxygen, inflammation, and nearby cells can protect cancer cells from treatment, making them harder to kill.

Importance of Finding Strategies to Attack Resistant Cancer Cells

  • Preserving Treatment Efficacy: Resistant cancer cells make treatments that used to work ineffective, lowering survival chances. Finding strategies to overcome resistance helps keep treatments working longer, improving patient outcomes.
  • Expanding Treatment Options: Overcoming resistance means more treatment options for patients. Clinicians can tailor treatment regimens to individual patients by targeting resistant cancer cells and optimizing therapeutic outcomes.
  • Enhancing Survival Rates: Effective strategies to attack resistant cancer cells prolong patient survival. By preventing or delaying disease progression, these strategies offer hope for better long-term outcomes.
  • Addressing Heterogeneity: Resistant cells within tumors vary, showing different resistance levels to specific treatments. Targeting resistant cells helps in reducing the likelihood of treatment failure and disease recurrence.

Current Strategies to Overcome Resistance

Researchers are exploring various innovative strategies to combat cancer cells that develop resistance to treatments. By understanding the underlying resistance mechanisms, these approaches aim to eliminate resilient cancer cells more effectively.

Here are some of the most promising methods being used today.

Targeting Cell-Cycle Kinase Inhibitors

Cell-cycle kinase inhibitors offer a promising solution against cancer resistance. These drugs slow or halt tumor growth by targeting cyclin-dependent kinases (CDKs). CDK inhibitors are effective, especially in hormone receptor-positive breast cancer, and reactivate natural tumor suppressors. 

Yet, cancer cells adapt, driving research into next-gen inhibitors targeting additional cell division enzymes. Consequently, early trials show potential for more effective, longer-lasting treatments, pushing researchers to innovate and outpace cancer’s adaptability for better patient outcomes.

Targeted Therapies

Targeted therapies focus on specific molecular targets linked to cancer. These treatments disrupt cancer cell growth and survival. For example, tyrosine kinase inhibitors (TKIs) block signals that make cancer cells grow. Even though resistance can occur through new mutations, targeted therapies like Imatinib for chronic myeloid leukemia (CML) and Trastuzumab for HER2-positive breast cancer have shown great success. They work best when combined with other treatments to help prevent resistance.

Combination Therapies

Combination therapies use multiple treatments to attack cancer cells from different angles, reducing the chance of resistance. This approach can include chemotherapy, targeted therapy, and immunotherapy. For example, combining BRAF and MEK inhibitors effectively treat melanoma by targeting different parts of the same pathway. This makes it harder for cancer cells to survive. Studies show that combination therapies improve response rates and extend progression-free survival, though managing side effects and interactions is important.


Immunotherapy uses the body’s immune system to fight cancer, making it a strong tool against resistant tumors. Checkpoint inhibitors like Pembrolizumab and Nivolumab block proteins that stop immune cells from attacking cancer. CAR-T cell therapy modifies a patient’s T-cells to target cancer more effectively and has been successful in certain blood cancers. Immunotherapy’s ability to adapt to cancer cells helps overcome resistance. Research is ongoing to enhance its effectiveness and manage side effects.


Nanotechnology uses nanoparticles to deliver drugs directly to cancer cells, increasing drug concentration at the tumor while reducing overall side effects. This approach can bypass resistance mechanisms like drug efflux pumps. Recent advances show that nanomedicine can improve the effectiveness of chemotherapy and targeted therapies.

Gene Editing and CRISPR

Gene editing tools like CRISPR can modify or correct genes responsible for cancer resistance. By targeting specific genes in resistance pathways, CRISPR can restore treatment sensitivity. Though still experimental, this technique shows promise for precision medicine despite ethical and technical challenges.

Emerging Experimental Treatments

New experimental treatments are being explored to fight resistant cancer cells. These include novel small molecules, antisense oligonucleotides, and adaptive therapy strategies. These innovative approaches are in various stages of research and trials, showing potential for future use in overcoming resistance.

Bottom Line

In our quest against cancer, resistant cancer cells stand as formidable opponents. Yet, with advancing knowledge and technology, we have potent weapons at our disposal. We’ve explored various strategies to combat resistance, from targeted therapies to immunotherapy and cutting-edge techniques like nanotechnology and gene editing.

Similarly, we at Globela, are open for collaboration across disciplines and borders, driven by the goal of defeating cancer. Globela’s Oncology department is committed to offering the highest quality products at affordable prices so that as many people as possible can benefit.

Whether you are a patient, a caregiver, or a healthcare professional, we are here to help you in your journey towards a cancer-free future.

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Transforming Metastatic Breast Cancer Treatment: The Critical Role of Independent Research

Metastatic breast cancer (MBC) is a serious and complex form of cancer that continues to challenge researchers and clinicians. While there have been advancements in treating early-stage breast cancer, MBC remains difficult to manage and treat effectively. Independent scientific research is crucial in finding new ways to understand and combat this disease.

This article explores the latest discoveries in MBC research, focusing on how independent studies make a real difference in patient care.


Metastatic breast cancer (MBC), or stage IV breast cancer, occurs when cancer spreads from the breast to other parts of the body like bones, liver, lungs, or brain. Unlike early-stage breast cancer, MBC isn’t curable and needs lifelong treatment. However, advancements in research are crucial for improving patient outcomes and quality of life.

Importance of Advancements in MBC Research

  • Improving Survival Rates: New treatments can help patients live longer.
  • Enhancing Quality of Life: Research leads to therapies that manage symptoms and reduce side effects.
  • Personalized Medicine: Discoveries enable tailored treatments based on individual genetics, improving effectiveness and reducing unnecessary treatments.
  • Understanding Metastasis: Insights into how and why cancer spreads can lead to new preventative measures and treatments.

The Current State of Metastatic Breast Cancer

MBC affects many individuals worldwide. In the United States, it is estimated more than 168,000 women will be living with metastatic breast cancer in 2020. Despite advances in detection and treatment, MBC remains a leading cause of cancer-related deaths among women, with a median survival of about three years after diagnosis.

Challenges in Treating MBC Compared to Early-Stage Breast Cancer

  • Complex Treatment: Early-stage breast cancer can often be treated with surgery and localized therapies. MBC requires systemic treatments like targeted therapy and immunotherapy to address cancer cells throughout the body.
  • Treatment Resistance: Metastatic cancer cells can develop resistance to treatments, reducing their effectiveness and necessitating new therapies and combinations.
  • Tumor Diversity: MBC tumors often contain different types of cancer cells, making it difficult to find a one-size-fits-all treatment. Different cells may respond differently to the same therapy.
  • Quality of Life: Managing MBC involves not only controlling cancer spread but also addressing symptoms and side effects, such as pain, fatigue, and emotional distress, which impact the patient’s quality of life.

The Role of Independent Scientific Research

Independent scientific research is conducted by researchers or organizations not directly affiliated with major institutions or government bodies. It is often funded by private foundations, non-profits, or individual donors, allowing for greater flexibility and innovation.

It is important for the following reasons:

  • Innovation and Flexibility: Independent researchers can explore new ideas and approaches that larger institutions might overlook.
  • Filling Knowledge Gaps: They can study areas that are often underfunded, contributing to a more complete understanding of MBC.
  • Collaboration and Cross-Disciplinary Work: Independent groups often work with other researchers, patients, and advocacy groups, fostering a comprehensive approach to finding solutions.
  • Rapid Response to Emerging Data: These researchers can quickly adapt to new findings, ensuring the latest discoveries are promptly investigated and translated into treatments.

Recent Breakthroughs in MBC Research

In the relentless pursuit of combating metastatic breast cancer (MBC), recent years have seen remarkable breakthroughs that are reshaping the landscape of treatment options and patient outcomes. These breakthroughs result from tireless efforts from independent researchers dedicated to unraveling the complexities of MBC.

Here’s a closer look at some of the most significant advancements:

On/Off Switch for MBC

In a recent study, researchers led by Lingyin Li, a Stanford biochemistry professor, found that the protein ENPP1 plays a key role in breast cancer’s resistance to immunotherapy and its spread. ENPP1 is found in both cancerous and healthy cells and is linked to immunotherapy resistance and metastasis in breast cancer patients.

Collaborating with UCSF professors, the team confirmed ENPP1’s predictive value in patient outcomes. Mouse studies showed that blocking ENPP1 reduced tumor growth and metastasis by suppressing the immune response. Dr Li suggested that ENPP1 acts like a “dam,” blocking immune signals and allowing cancer cells to hide.

These findings could help guide treatment decisions and improve therapies for breast cancer and other cancers that evade the immune system.

Two-pronged Immunotherapy for Metastatic Breast Cancer

Researchers at Washington University School of Medicine have found a way to make metastatic breast tumors in bone susceptible to the body’s immune system. By boosting certain immune cells, they cleared breast tumors in mice and prevented them from returning.

Blocking a molecule called p38 MAPK made the tumor area more vulnerable while combining it with an immune therapy called OX40 agonist supercharged T cells, effectively eliminating metastatic tumors.

This approach shows promise for treating metastatic breast cancer and protecting against bone loss. Clinical trials are ongoing for the therapies involved.

Targeting SMYD2 Protein to Prevent MBC

In a study published in Cell Discovery, researchers led by a biologist at CNRS have uncovered a potential breakthrough in understanding metastatic breast cancer. They found that a protein abundant in aggressive breast cancers, SMYD2, might play a pivotal role in promoting metastasis. This protein appears to activate BCAR3, another protein known for aiding cancer cell adhesion and migration.

Through experiments on mice with early-stage breast cancer, inhibiting SMYD2 prevented metastasis, suggesting a promising avenue for early treatment strategies that could potentially improve patient outcomes.

Translating Research into Patient Care

Recent progress in metastatic breast cancer (MBC) research is bringing hope to patients. Turning research into practical treatments follows a step-by-step process:

  • Lab Testing: New treatments are first tested in labs to make sure they’re safe and effective.
  • Clinical Trials: Promising treatments move to human trials, starting small to check safety and dosage, then expanding to see how well they work.
  • Regulatory Approval: Once proven safe and effective, treatments get approval from organizations like the FDA.
  • Guidelines and Monitoring: Approved treatments become part of official guidelines for doctors. They’re also watched closely to make sure they keep working well and are safe in the long run.

Bottom Line

Independent research is vital for advancing our understanding and treatment of metastatic breast cancer (MBC). Despite challenges, researchers have made significant breakthroughs, improving patient care. To sustain progress, we must support independent research efforts through funding and advocacy.

Looking ahead, personalized medicine offers hope for better outcomes. Let’s continue prioritizing and investing in independent research to provide hope and better solutions for MBC patients.

Cancer blog-min

The Importance of Early Detection and Prevention of Cancer


Health is indeed the greatest wealth one can have.  Being vigilant towards the health of yourself and your loved ones is a top priority. This involves routine health check-ups and regular monitoring required as per physician’s advice relevant to an individual’s medical history. Any disturbance found in the body’s normal rhythm can hence be caught at an early stage and appropriate measures can be taken for its treatment and/or management. Amongst other ailments, cancer diagnosis can be most terrifying. Since there is no definite cure for Cancer, early stage diagnosis can greatly help in better treatment outcome and improved Quality of life.

Role of early diagnosis & screening-

The two main components of early detection of cancer are, i) early diagnosis and ii) screening. Early diagnosis focuses on detecting symptomatic patients as early as possible, while screening refers to the use of tests performed to detect cancer early on healthy individuals who have not yet shown symptoms of disease and are asymptomatic. The aim of screening is to reduce ailments and mortality caused by cancer. It is an effective method which is widely accepted and beneficial to people who are at risk with regards to cancer. This is crucial as it is one of the first actions taken to prevent disease. Furthermore, patients whose cancer is detected at an early stage possess a higher chance of cured disease, complete recovery, increased quality of life and longevity. Efforts to improve the selection of candidates for cancer screening, in order to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the field over time.

Goals of early detection- 

The goal of cancer screening and early detection is to cure cancer by detecting the malignancy, or its precursor lesion, at an early stage prior to the onset of symptoms, when treatment of cancer is most effective. Indeed, overall cancer mortality has decreased by 25% from 1990 to 2015 for the United States U.S.), with even greater declines in the mortality rates for colorectal cancer (47% among men and 44% among women) and breast cancer (39% among women). A portion of this decrease can be attributed to the introduction of high-quality cancer screening for colorectal and breast cancer. The most successful cancer screening programs lead to the identification of precursor lesions (e.g., cervical intraepithelial neoplasia (CIN) with cervical cancer screening and colonic polyps with colorectal cancer screening) where the treatment of the precursor lesion leads to a decrease in the incidence of invasive and lethally spreading cancer over a period of time.

Application of various Imaging techniques-

Imaging tests used in diagnosing cancer may include Computed tomography (CT) scan, Magnetic resonance imaging (MRI) scan, Breast MRI, X-rays and other radiographic tests, Mammography, Nuclear medicine scans (bone scans, PET scans, Thyroid scans, MUGA scans, gallium scans), Ultrasound. Imaging tests are only part of cancer diagnosis and treatment. A complete cancer work-up includes assessment of medical history by a certified health care professional, a thorough physical exam, blood work and other lab tests.

Biopsy & its types-

Biopsy is another method that aids in detection of Cancer. It is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The most common types of biopsy includes: (1) Incisional biopsy, in which only a sample, part of affected tissue is removed; (2) Excisional biopsy, in which an entire lump or suspicious area is removed; and (3) Needle biopsy, in which a sample of tissue or fluid is removed through a needle aspiration. Depending on the type of needle used, the procedure is called a core biopsy when performed with a wide needle, and fine-needle aspiration biopsy when a thin needle is used.

Genetic & DNA testing-

Genetic testing is another effective method in Screening for Cancers. It helps in discovering certain mutations (changes) in genetic make-up of an individual, which are more prone to getting certain cancers. The most commonly mutated gene in people with cancer is p53 or TP53. More than 50% of cancers involve a missing or damaged p53 gene. Most p53 gene mutations are acquired. Germ line p53 mutations are rare, but patients who carry them are at a higher risk of developing many different types of cancer.

Routine examinations required to check for warning signs that may lead to Cancer-

There are few warning signs and symptoms that should not be neglected for better health. They are as follows:

-A sore that does not heal, delayed or slow healing

-Unusual bleeding or discharge.

-Thickening or lump in breast or elsewhere.

-Indigestion or difficulty in swallowing.

-Obvious change in wart or mole.

-Nagging cough or hoarseness.

 -A change in bowel habits, including diarrhoea, constipation or consistency of your stool.

-Persistent abdominal discomfort such as cramps, gas or pain.

-Rectal bleeding or blood in your stool.

-Unexplained weight loss.

-Weakness or fatigue, which does not get better after adequate rest.

Importance of early diagnosis and its comparison with late stage diagnosis; along with their respective prognosis-

Lack of early screening leads to late stage diagnosis. In most cases, patients who are diagnosed with cancer at earlier stages show improved survival, clinical outcomes and better quality of life. However, screening for earlier cancer detection remains limited. As of year 2021, broad-based cancer screenings for asymptomatic patients are recommended in the US for just 5 cancer types (breast, cervical, colorectal, lung for a high-risk subset of the population, and prostate).Statistically, 71% of all cancer mortality is from cancers that lack broad-based screenings for asymptomatic patients. Thus, earlier cancer diagnosis results in improved survival. Patients diagnosed with earlier stages of cancer (stage I-II) generally have a higher likelihood of recovery than those diagnosed at a later stage (stage III-IV). For non-small cell lung cancer (NSCLC), stomach, and pancreatic cancers, between 36% and 53% of patients are diagnosed with stage IV cancer, where the cancer has spread to other parts of the body, decreasing survival chances. The 5-year survival rate for non-small-cell lung cancer (NSCLC), stomach, and pancreatic cancers, doubles in all cases when detected at earlier stages. These differences in survival rates emphasize the opportunity to make progress in beating cancer by decreasing late-stage diagnoses with improved and expanded screenings.

Suffering patients progress through more extensive treatment demanded by later stage diagnosis. Quality of life goes down including through physical, emotional, and social functioning. Late-stage diagnosis often requires more intensive and more invasive interventions that result in sometimes difficult and lasting side effects. For example, patients with late-stage NSCLC diagnosis often suffer from dyspnoea, or laboured breathing, after their treatment is complete. Similarly, stomach cancer patients recovering from a partial or full gastrectomy followed by other treatments such as chemotherapy, radiation, and immunotherapy in late stages may suffer from chronic fatigue, difficulty eating, and challenges performing everyday activities.


A plan for early diagnosis is a key component in controlling and preventing cancer. Main goal is to cure cancer patients, prolong their life considerably while ensuring a good quality of life. Treatment plans need to be integrated with a palliative care programme, so that patients with advanced cancers, who can no longer benefit from treatment, will get adequate relief from their physical, psychosocial and spiritual suffering. Additionally, programmes should include an awareness-raising component, to encourage and educate patients, family and community members about the cancer risk factors and the need for taking preventive measures to avoid contracting cancer.