Just as cancer evolves, so do the treatments for the disease – which is great news for cancer patients

Former U.S. president Jimmy Carter passed away on Dec. 29, 2024, after celebrating his 100th birthday a few months earlier. In 2015, it was discovered that his malignant melanoma had metastasized to his brain. With the old standard therapy of just a few years ago, he would have been treated with chemotherapy plus radiation to the brain – and he would have been lucky to have survived six months.

Instead, president Carter was treated with the immunotherapy drug pembrolizumab, which the FDA had approved the year before for this indication.

This is one example of new anticancer therapies that have been developed in the last few years and have significantly improved cancer patients’ survival rates. Other factors that have improved the survival rates of cancer patients include more effective early screening methods of detecting early-stage cancer, and the decreased incidence of smoking.

According to a recent American Cancer Society report, the overall five-year cancer survival rate has increased from 49% in the mid-1970s to 68% currently.

Here are some notable cancers which have seen improved survival rates.

The New Therapies Timeline – Highlights

  • 1990: FDA approves the use of BCG to treat superficial bladder cancer
  • 1997: FDA approves Rituximab, the first targeted therapy for B-cell lymphomas
  • 1999: Trastuzumab becomes the first targeted therapy for breast cancer
  • 2001: FDA approves Imatinib to treat chronic myeloid leukemia and other rare gastrointestinal tumors
  • 2003: Gefitinib became the first targeted therapy approved for non-small cell lung cancer
  • 2004: Bevacizumab became the first anti-angiogenic drug; it targeted the blood supply to tumors. Erlotinib expands options for NSCLC patients
  • 2005: Sorafenib is approved for renal cell carcinoma (kidney cancer) and eventually to treat hepatocellular carcinoma (liver cancer)
  • 2011: CAR-T cell therapy is approved for leukemia treatment. It combines gene therapy with immunotherapy
  • 2014: FDA approved the immunotherapy drugs pembrolizumab and nivolumab to treat malignant melanoma. It also approved oral targeted agents trametinib and dabrafenib for BRAF-mutant melanoma
  • 2014: FDA approved nine-valent Gardasil 9 vaccine for broader protection against HPV strains associated with cervical cancer
  • 2015: FDA approved T-VEC oncolytic virus to treat malignant melanoma
  • 2021: FDA approved Delytact oncolytic virus to treat malignant glioma
  • 2024: In February, the FDA approved lifileucel, the first cancer treatment that uses immune cells called tumor-infiltrating lymphocytes. Lifileucel is the first cellular therapy to be approved for a solid tumor, malignant melanoma
  • 2024: In August, the FDA approved T-receptor receptor therapy. It is a somewhat different type of cellular and gene therapy compared to CAR-T therapy. It was approved to treat synovial cell sarcoma
  • 2025: The FDA continues to approve drugs at a remarkably high rate. For example, in February 2025, more than half-dozen drugs were approved including 67Cu-SAR-bisPSMA for treating adult patients with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer

In terms of drug therapy, the classical therapies include chemotherapy and hormonal therapy.

Chemotherapy

Chemotherapies are drugs whose aim is to destroy rapidly growing cells, such as cancer cells. However, because normal cells also need to grow, and some grow quite rapidly (such as those in the bone marrow and those lining the mouth and intestine), all chemotherapy agents affect normal cells and cause resulting side effects.

Most newer drugs are designed to target cancer cells rather than normal cells. This allows for an increased effective dose to be delivered, by decreasing the toxicity to normal cells. There are more than 100 chemotherapy drugs currently available.

Hormones

Hormones are proteins produced by endocrine glands that affect activities of target tissues and organs. Some cancers, especially some breast cancers and some prostate cancers, grow and spread more when they are exposed to certain hormones. Reversing the effects of these hormones may control these cancers.

Endocrine therapy may be used alone or combined with other types of cancer therapy, such as targeted therapy. It is worth noting that hormone therapy is a type of targeted therapy.

Newer Therapies

Gene Therapies

Gene therapy involves the replacement of a defective gene with a functional, healthy copy of that gene, in either the cancer cell or in the immune cell.

CAR-T Therapy

CAR-T cell therapy is considered an immunotherapy and a gene therapy regimen. CAR-T cells are generated by removing T cells from a patient’s blood, engineering the cells in the lab to express the CAR (chimeric antigen receptor) recognizing the tumor antigen of interest, and then reinfusing those cells back into the patient.

CAR-T cell therapy is used to treat various conditions including certain types of lymphomas and leukemias, as well as multiple myeloma. With CAR-T cell therapy, about 70% to 90% of people with lymphoma experience remission (i.e. becoming cancer free). It is offered to patients whereby classical chemotherapy and also bone marrow or stem cell transplant therapies fail. Studies are now ongoing looking at CAR-T therapy for the treatment of solid tumors, but to date, CAR-T treatment has not yet been proven to be effective in treating these cancer types.

This is an extremely expensive therapy, perhaps $1,000,000.

Other Therapies

In the U.S., FDA-approved gene therapy products for cancer include:

  • Axicabtagene ciloleucel (Yescarta). This gene therapy is for adults who have certain types of large B-cell lymphoma that don’t respond to treatment
  • Talimogene laherparepvec (Imlygic). This gene therapy is used to treat certain types of tumors in people with melanoma that come back after surgery
  • Tisagenlecleucel (Kymriah). This gene therapy is for people up to 25 years old who have follicular lymphoma that has come back or isn’t responding to treatment

Targeted Therapies

Targeted cancer therapies are drugs or other substances with interchangeable terms such as “molecularly targeted drugs,” “molecularly targeted therapies,” and “precision medicines.” Those drugs are designed to interfere with certain molecules in the cancer cell to block cancer growth and spread.

Targeted therapy drugs are different from standard chemotherapy drugs in that they attack cancer cells while doing little or no damage to normal cells. In 2006, only 5.3% of American cancer patients received targeted therapy. By 2020, that number had more than doubled to 13.6%.

But even if a person’s cancer cell has a certain target, it doesn’t mean that targeted therapy will always work. Even if it works, often it is not curative. That’s why targeted therapy is sometimes combined with other treatments such as surgery, chemotherapy, or radiation therapy.

Types of Targeted Therapies

Classes of these drugs include monoclonal antibodies, apoptosis-inducing drugs, angiogenesis inhibitors (such as bevacizumab), mTOR inhibitors, PARP inhibitors, and small molecular kinase inhibitors.

But the type of targeted drug which is getting the most hype in the community is immunotherapy**.**

Immunotherapy

Cancer cells find ways to evade the immune system. They have increased levels of certain proteins on their surface that attach to and activate “brakes” on T cells, thus stopping them from attacking cancer cells.

These brakes are called immune checkpoint proteins. They release the brakes on T cells and trigger previously restrained T cells to attack and destroy cancer cells.

The use of immunotherapy has markedly improved the outcome in many patients.

Some of these drugs (but far from a comprehensive list) include atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, etc.  These medications are used to treat many types of cancer, including some types of lymphoma, lung, kidney, bladder, gynecologic, and melanoma.

One evidence of the widespread use of immunotherapy is that in 2023, the worldwide sales of pembrolizumab reached $25 billion – the top-selling medical drug that year!

T Cell Engagers

T cell engagers are considered a special form of immunotherapy.  They use engineered antibodies to link T cells to cancer cells, essentially “redirecting” the immune response without altering the T cell’s DNA at its core. These include:

Antibody-Drug Conjugates

With this novel design, chemotherapy is now attached to a monoclonal antibody directed at a surface tumor antigen, allowing for the delivery of extremely high levels of chemotherapy directly to the tumor bed. Therefore, this molecule has a dual anticancer function: that of a chemotherapy drug and that of a monoclonal antibody.

As of October 2023, the FDA has approved at least 15 such molecules for a variety of tumor types.

Cancer Vaccines

All vaccines work by training one’s immune system to defend the body against foreign invaders or abnormal cells that pose a threat, such as cancer cells.

There are two cancer vaccines use to prevent cancer. These include the Human Papillomavirus Vaccine (HPV) and Hepatitis B vaccine. The HPV vaccine is used to prevent HPV infection, which can lead to several types of cancer, including cervical cancer, head and neck cancers, anal cancer etc. The Hepatitis B virus protects against Hepatitis B chronic liver disease, which can increase the risk of hepatocellular (liver) cancer.

Several therapeutic cancer vaccines are already in use for different cancers:

  • Prostate Cancer Vaccine: Sipuleucel-T (Provenge®) is used for castrate resistant (i.e. hormone resistant)
  • Bladder Cancer Vaccines-Bacillus Calmette-Guérin (BCG) is used to treat early-stage bladder cancers. It is made from inactivated tuberculosis bacteria. Nadofaragene firadonevec (Adstiladrin®) is approved for treatment of early-stage bladder cancers that have progressed despite BCG therapy. Like BCG, it is delivered into the urinary bladder via a cystoscopy procedure
  • Melanoma Vaccine: T-VEC (Imlygic®) is an oncolytic (i.e. cancer destroying) virus-based vaccine that is used to treat advanced melanoma that cannot be completely removed with surgery. It is injected into some melanoma tumors – then an immune response may develop that is directed at both the injected and the non-injected melanoma tumors

Radionuclides/Radiopharmaceuticals

Another treatment option available for certain types of cancer is the use of targeted radionuclide therapy, which is based on administering radioactive substances to patients. Just like chemotherapy, this therapy is a systemic treatment which means that such agents reach cells throughout the body by travelling through the bloodstream. However, unlike chemotherapy, these radioactive substances specifically target diseased cells, thus reducing potential side effects. Often in these scenarios, other drugs (chemotherapy or other targeted therapies) are not all that effective.

Approved therapies in the U.S.A. include:

  • Lutetium Lu 177 (vipivotide tetraxetan) is used for the treatment of prostate-specific membrane antigen­-­positive metastatic castration-resistant prostate cancer. Lutetium 177 dotatate is used for the treatment of somatostatin receptor-positive gastro-entero-pancreatic-neuroendocrine tumors
  • Iodine-131 can treat certain types of thyroid cancers
  • Radium-223 dichloride is effective at treating bone tumors when prostate cancer has spread to patients’ bones

Surgical/Invasive Procedures

There are other non-medical new treatments. I will mention briefly mention these treatments – but description of these treatments is possible in only a separate article.

These include Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Trans-arterial Chemoembolization (TACE), Trans-arterial regional radio-embolization (TARE), organ transplants (including liver and bone marrow or stem cell transplants), Radiofrequency Ablation (RFA), Cryoablation etc.

Why Clinical Trials Matter

Clinical trials are research studies that allow patients to access some of the newest, most innovative treatments that are not otherwise available outside the study. It is through such trials that more effective new treatments are discovered and eventually approved by the FDA or other countries’ regulatory authorities for standard of care use by oncologists and other cancer treating healthcare professionals.

Most of today’s standard cancer treatments were investigated by these clinical trials at one time. Without clinical trials, most of the newer therapies discussed earlier would not have been available.

Patients interested in pursuing such new treatments in clinical trials, can find the availability of such trials suitable for their cancer by looking at Clinicaltrials.gov or by calling the National Cancer Institute Information Service 1-800-4-CANCER (1-800-422-6237) and dialing option 2.